Expression and regulatory function of miRNA-182 in triple-negative breast cancer cells through its targeting of profilin 1.

We aimed to evaluate the expression of microRNA-182 (miR-182) in triple-negative breast cancer (TNBC) tissues and the TNBC cell line MDA-MB-231 and to investigate the effects of mirR-182 on the cellular behavior of MDA-MB-231 and the expression of the target gene profilin 1 (PFN1), thus providing new methods and new strategies for the treatment of TNBC. Quantitative real-time PCR (qRT-PCR) was utilized to evaluate the expression of miR-182 in TNBC tissues, relatively normal tissues adjacent to TNBC and the TNBC cell line MDA-MB-231. Forty-eight hours after the MDA-MB-231 cells were transfected with the miR-182 inhibitor, qRT-PCR was utilized to detect the changes in miR-182 expression levels, and an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was utilized to determine the effects of miR-182 on cell viability. Flow cytometry was adopted to determine whether miR-182 affects the proliferation rates and apoptosis levels of the MDA-MB-231 cells. The transwell migration assay method was used to investigate the effects of miR-182 on the migration of the MDA-MB-231 cells. A luciferase reporter gene system was applied to validate that PFN1 was the target gene of miR-182. Western blot was used to measure the effects of miR-182 on the PFN1 protein expression levels in the cells. qRT-PCR results showed that compared with the relatively normal tissues adjacent to TNBC, miR-182 expression was significantly increased in the TNBC tissues and the MDA-MB-231 cells (p<0.01). Compared with the control group, MDA-MB-231 cells transfected with the miR-182 inhibitor and incubated for 48 h showed significantly decreased miR-182 expression (p<0.01). The results of an MTT assay showed that inhibition of miR-182 in MDA-MB-231 cells led to significantly reduced cell viability (p<0.05). Flow cytometry analysis indicated that inhibition of miR-182 expression resulted in significantly decreased cell proliferation (p<0.05) and significantly increased levels of apoptosis (p<0.05). The results of a transwell migration assay showed that after inhibited of miR-182 expression, the number of cells passing through the transwell membranes was significantly decreased (p<0.05). The results from a luciferase reporter gene system showed that compared with the control group, the relative luciferase activity of the group transfected with the miR-182 inhibitor was significantly increased (p<0.05). Western blot analysis showed that compared with the control group, PFN1 protein expression levels were significantly increased in the MDA-MB-231 cells transfected with the miR-182 inhibitor and incubated for 48 h (p<0.05). In conclusion, miR-182 is upregulated in TNBC tissues and cells. It promotes the proliferation and invasion of MDA-MB-231 cells and could negatively regulate PFN1 protein expression. Treatment strategies utilizing inhibition of miR-182 expression or overexpression of the PFN1 gene might benefit patients with TNBC.

BTG2 inhibits the proliferation, invasion, and apoptosis of MDA-MB-231 triple-negative breast cancer cells.

The purposes of this study were to investigate the effects of B cell translocation gene 2 (BTG2) on the proliferation, apoptosis, and invasion of triple-negative breast cancer and to provide an experimental basis for the future treatment of human triple-negative breast cancer. A pcDNA3.1-BTG2 eukaryotic expression vector was constructed and transfected into the MDA-MB-231 human triple-negative breast cancer cell line using lipofection. Then, relevant changes in the biological characteristics of the BTG2-expressing cell line were analyzed using MTT (tetrazolium blue), flow cytometry, and Transwell invasion chamber assays. Additionally, the effects of BTG2 expression on cyclin D1, caspase 3, and matrix metalloproteinases 1/2 (MMP-1/-2) expression were analyzed. Cell proliferation was significantly lower in the pcDNA3.1-BTG2-transfected group compared to the empty vector and blank control groups (p<0.05). There was no significant difference between the empty vector and blank control groups. FCM results demonstrated that there were significantly more cells in the G1 phase of the cell cycle and fewer S phase cells in the pcDNA3.1-BTG2 group than in the empty vector and blank control groups (p<0.05). Additionally, the proportion of cells that migrated across the membrane was significantly lower in the pcDNA3.1-BTG2 group than in the empty vector and blank control groups (p<0.05). Cyclin D1 and MMP-1/-2 expression were significantly lower in MDA-MB-231 cells transfected with pcDNA3.1-BTG2 as compared to the empty vector and blank control groups (p<0.05). Caspase 3 expression was significantly higher in MDA-MB-231 cells from the pcDNA3.1-BTG2 group compared to the empty vector and blank control groups (p<0.05). In conclusion, BTG2 may inhibit MDA-MB-231 proliferation and promote apoptosis. Additionally, BTG2 may also inhibit the invasion of MDA-MB-231 human triple-negative breast cancer cells.

Predicting the recurrence-free survival of phyllodes tumor of the breast: a nomogram based on clinicopathology features, treatment, and surgical margin.

Background: Grading based on histopathologic indicators cannot accurately assess the prognosis of phyllodes tumor (PT) of the breast. This article aimed to investigate the correlation between PT prognosis and clinicopathological features, treatment, and surgical margin. Methods: The clinicopathological data of patients with pathologically confirmed PT at our institution were retrospectively collected. Univariate and multivariate Cox proportional risk models were employed to test the effects of different variables on the prognosis of PT. A nomogram to predict the 1-, 3-, 5-, and 10-year recurrence-free survival (RFS) of PT was proposed, and its discriminative ability and calibration were tested using the concordance index (C-index), area under the curve (AUC), and calibration plots. All statistical analyses were performed using R. Results: A total of 342 PT patients were included, including 242 benign (70.8%), 75 borderline (21.9%) and 25 malignant (7.3%) cases. The median follow-up period was 64.5 months (range, 3-179 months), 66 PT patients had local recurrence (LR), and four patients had distant metastasis. The 1-, 3-, 5-, and 10-year RFS of the PT patients were 90.8%, 81.8%, 78%, and 76.7%, respectively. Age, fibroadenoma (FA) surgery history, treatment, mitotic activity, and surgical margin were selected as the independent factors for PT prognosis. The nomogram showed good discriminative ability and calibration, as indicated by the C-index [0.78, 95% confidence interval (CI): 0.75-0.11]. Conclusions: Independent predictors related to PT prognosis were selected to establish a nomogram for predicting the RFS of PT. This nomogram was able to objectively stratify PT patients into prognostic groups and performed well in the internal validation.

Contralateral prophylactic mastectomy for unilateral breast cancer in Chinese female population: a retrospective cohort study.

Background: Due to differences in socioeconomic and cultural backgrounds, the characteristics and prognosis of Asian female patients choosing contralateral prophylactic mastectomy (CPM) are likely to be different from Western patients. To fill the research gap of CPM in Asian populations, this study aims to explore the application trend, survival benefits, decision-making factors, and satisfaction of CPM based on the Chinese patients undergoing CPM. Methods: The 0-III stage unilateral breast cancer (UBC) patients who received breast surgery in the Chinese PLA General Hospital from 2005 to 2017 were selected. The surgical procedures included simple mastectomy (SM), nipple-sparing mastectomy (NSM), breast conserving surgery (BCS), and CPM. Cox proportional regression analyses and Kaplan-Meier (KM) curve were performed to compare the overall survival (OS) and disease-free survival (DFS) rates between CPM group and unilateral mastectomy (UM) group. Proportional propensity score matching (PSM) with a 1:1 ratio was used to match the two groups and secondary survival analysis was performed. Logistic regression models were used to test predictive factors related to patients' CPM surgical decision-making. Results: Four thousand two hundred and seventy-six patients were included in the study, with 73 patients receiving CPM, 3,567 receiving SM, 151 receiving NSM, and 485 receiving BCS. CPM surgery was first used in 2007, with a peak application rate of 3.02% in 2016. Three thousand seven hundred and ninety-one patients were included in the survival analysis, with a median follow-up time of 66.60 months. Compared to UM patients, neither the KM survival curve nor Cox regression hazard analyses of CPM showed better OS (P=0.963; P=0.834). After PSM, CPM also did not exhibit significant survival benefits in OS (P=0.335) and DFS (P=0.409). The logistic regression analyses showed that NSM surgery and lower tumor-node-metastasis (TNM) stage were independent factors to promote the CPM decision-making of patients. The CPM group showed high overall satisfaction (84.9%) and relatively low appearance satisfaction (69.9%). Conclusions: CPM was practiced for the first time since 2007 in our hospital. CPM does not provide any OS and DFS benefits compared to UM and the appearance satisfaction procedure was relatively low. Therefore, clinicians should fully communicate with patients before surgery and be more cautious in giving CPM recommendations.

Breast-conserving therapy versus mastectomy for breast cancer: a ten-year follow-up single-center real-world study.

Background: The rapid development of early diagnostic methods and systematic treatment for breast cancer have shed lights on the insight of prognosis of breast-conserving therapy versus mastectomy. However, there are relatively few studies with long-term follow-up, large patient cohort and under the contemporary setting in China on the subject of survival of patients undergoing breast conserving therapy versus mastectomy. Methods: Data on the cases of breast-conserving therapy and mastectomy for breast cancer from October 1, 2005 to September 31, 2010 were retrieved from the breast cancer database of Chinese PLA General Hospital. The clinicopathological characteristics of patients were compared by chi-square test or Fisher's exact test. Breast cancer-specific survival, disease-free survival, local recurrence-free survival, loco-regional recurrence-free survival, and distant metastasis-free survival were calculated and compared by Kaplan-Meier survival analysis and log-rank test firstly. And then Cox Proportional-Hazards model was used for multivariate analysis. Results: There were 296 patients in the breast-conserving surgery group and 675 patients in the mastectomy group. For patients with invasive breast cancer in the entire cohort, the 10-year breast cancer-specific survival rate of patients in the breast-conserving surgery group at stage I-II was significantly higher than that of the mastectomy group. However, surgical method was not an independent prognostic factor for breast cancer-specific survival, disease-free survival and local recurrence-free survival. Moreover, N stage and luminal B-like subtype were independent prognostic factors for the breast cancer-specific survival of invasive breast cancer in the entire cohort. Conclusions: This study suggests that there is no significant difference in breast cancer-specific survival between breast cancer patients undergoing breast-conserving surgery and mastectomy after adjusting for confounding factors. Lymph node staging is the major risk factor affecting patients' survival. In this case, choosing patients with smaller tumor size, avoiding patients with stage N3, and removing a smaller volume of breast tissue including tumors while ensuring negative margins may reduce the patient's risk of local recurrence and loco-regional recurrence.

Clinicopathological features and prognosis of bilateral breast cancer: a single-center cohort study based on Chinese data.

Background: The incidence of bilateral breast cancer (BBC) is low, accounting for 5% of patients with breast cancer. This study aimed to investigate the clinicopathological features and prognosis of synchronous bilateral breast cancer (SBBC) and metachronous bilateral breast cancer (MBBC) in the Chinese population. Methods: Patients with BBC, including SBBC and MBBC, were selected from 6,162 breast cancer patients who underwent surgery at the Chinese People's Liberation Army (PLA) General Hospital between January 2007 and December 2019. Furthermore, patients with unilateral breast cancer (UBC) who underwent surgery at the same time were randomly selected at a ratio of 1:2 as the control group. Clinicopathological features and prognosis were compared between the groups. Results: In all, 123 (2.0%) patients with BBC were enrolled in this study, including 98 (1.6%) SBBC and 25 (0.4%) MBBC patients. A total of 280 patients with UBC were selected for the control group. Compared with patients with UBC, patients with SBBC were more likely to be older and have a family history of breast cancer, non-infiltrative carcinoma, lower pathological tumor-node-metastasis (pTNM) stage, and luminal A type breast cancer as their first tumor. Patients with MBBC were more likely to be postmenopausal and have hormone receptor [estrogen receptor (ER)/progesterone receptor (PR)] negativity, a higher pTNM stage, and a triple-negative first tumor. Patients with UBC with ER/PR (-) were more likely to develop contralateral breast cancer (CBC) than those with ER/PR (+). There was no significant difference in overall survival (OS) and disease-free survival (DFS) between patients with SBBC and patients with UBC. Patients with MBBC had worse DFS than those with UBC, but OS was similar for both types of patients. Patients with MBBC <55 years at first diagnosis had significantly shorter DFS compared to those with SBBC and UBC. A multivariate Cox proportional hazards model revealed that age ≥55 years and ER/PR negativity of the first tumor were independent risk factors for OS. Independent risk factors for DFS included MBBC, age <55 years, family history of other malignant tumors, ER/PR (-), lymphovascular invasion, and N stage ≥2 of the first tumor. Conclusions: The OS and DFS of patients with SBBC and UBC were similar. The MBBC patients, especially those <55 years old at first diagnosis, had shorter DFS than patients with UBC.

External verification and improvement of the Neo-Bioscore staging system in a Chinese cohort.

Background: Accurately predicting outcomes for patients with breast cancer receiving neoadjuvant chemotherapy (NAC) is critical for clinical decisions. Prognostic models applicable to the Chinese population remain limited. The Neo-Bioscore staging system has been utilized as a predictive model for survival of breast cancer patients after NAC. This study aimed to validate the applicability of Neo-Bioscore in a Chinese population and develop an improved staging system based on it to predict prognosis of Chinese patients more accurately. Methods: This study retrospectively collected clinicopathological and survival data in patients receiving NAC from February 2005 to August 2018 in PLA General Hospital. Discrimination, calibration and clinical usefulness were used to assess model performance. Univariate and multivariate analyses assessed relationships between clinicopathological factors and disease-specific survival. For model modification, postoperative pathological staging in the Neo-Bioscore was substituted with the posttreatment pathological tumor (ypT) stage and posttreatment pathological lymph node (ypN) stage. Neo-Bioscore and Modified Neo-Bioscore were compared with the American Joint Committee on Cancer (AJCC) staging system. Results: A total of 436 patients with a median follow-up of 67 months were included. Five-year disease-specific survival (DSS), overall survival, and disease-free survival rates were 88.0%, 87.9%, and 76.8%, respectively. The concordance index (C-index) of the Neo-Bioscore staging system, posttreatment pathological stage (PS), and pretreatment clinical stage (CS) for DSS were 0.78 [95% confidence interval (CI): 0.72-0.83], 0.75 (95% CI: 0.69-0.82), and 0.68 (95% CI: 0.62-0.74), respectively. No significant difference between the Neo-Bioscore and PS was observed in the C-index (P=0.399). ypT and ypN were included in Neo-Bioscore to replace PS and create a modified staging system named MNeo-Bioscore. The C-index for DSS of the MNeo-Bioscore was 0.82 (95% CI: 0.78-0.87), and the calibration curve and decision curve analysis (DCA) curve performed well in internal validation. Conclusions: The Neo-Bioscore staging system provided precise prognostic stratification for Chinese breast cancer patients receiving NAC; ypN and ypT stage may be substituted for PS to add significant prognostic value for Neo-Bioscore.

A simplified scoring protocol to improve diagnostic accuracy with the breast imaging reporting and data system in breast magnetic resonance imaging.

Background: The breast imaging reporting and data system (BI-RADS) lexicon provides a standardized terminology for describing leision characteristics but does not provide defined rules for converting specific imaging features into diagnostic categories. The inter-reader agreement of the BI-RADS is moderate. In this study, we explored the use of a simplified protocol and scoring system for BI-RADS categorization which integrates the morphologic features (MF), kinetic time-intensity curve (TIC), and apparent diffusion coefficient (ADC) values with equal weights, with a view to providing a convenient and practical method for breast magnetic resonance imaging (MRI) and improving the inter-reader agreement and diagnostic performance of BI-RADS. Methods: This cross-sectional, retrospective, single-center study included 879 patients with 898 histopathologically verified lesions who underwent an MRI scan on a 3.0 Tesla GE Discovery 750 MRI scanner between January 1, 2017, and June 30, 2020. The BI-RADS categorization of the studied lesions was assessed according to the sum of the assigned scores (the presence of malignant MF, lower ADC, and suspicious TIC each warranted a score of +1). Total scores of +2 and +3 were classified as category 5, scores of +1 were classified as category 4, and scores of +0 but with other lesions of interest were classified as category 3. The receiver operating characteristic (ROC) curves were plotted, and the sensitivity, specificity, and accuracy of this categorization were investigated to assess its efficacy and its consistency with pathology. Results: There were 472 malignant, 104 risk, and 322 benign lesions. Our simplified scoring protocol had high diagnostic accuracy, with an area under curve (AUC) value of 0.896. In terms of the borderline effect of pathological risk and category 4 lesions, our results showed that when risk lesions were classified together with malignant ones, the AUC value improved (0.876 vs. 0.844 and 0.909 vs. 0.900). When category 4 and 5 lesions were classified as malignant, the specificity, accuracy, and AUC value decreased (82.3% vs. 93.2%, 89.3% vs. 90.2%, and 0.876 vs. 0.909, respectively). Therefore, to improve the diagnostic accuracy of the protocol for BI-RADS categorization, only category 5 lesions should be considered to be malignant. Conclusions: Our simplified scoring protocol that integrates MF, TIC, and ADC values with equal weights for BI-RADS categorization could improve both the diagnostic performance of the protocol for BI-RADS categorization in clinical practice and the understanding of the benign-risk-malignant breast diseases.

Surgical management and prognosis of phyllodes tumors of the breast.

Background: Regardless of histological grade, phyllodes tumors (PTs) exhibit the potential of local recurrence. The National Comprehensive Cancer Network (NCCN) recommends wide local excision (WLE) with a 1 cm margin or more for borderline/malignant PTs but excisional biopsy for benign PTs. However, the treatment of benign PTs remains controversial and the clinicopathologic risk factors for the local recurrence is still unclear. Methods: We retrospectively analyzed 238 patients with PTs who underwent surgery at the Chinese PLA General Hospital from January 1, 2006 and April 30, 2020. We stratified our analysis according to histologic grade and explored the clinicopathologic factors to influence local recurrence (LR), including age, histologic grade, history of fibroadenoma, type of surgery [vacuum-assisted biopsy system (VABS), local excision (LE), wide local excision (WLE) and mastectomy]. Results: All 238 cases were categorized as benign (171, 71.8%), borderline (38, 16.0%), or malignant (29, 12.2%). The median follow-up was 50.2 months. In multivariate analysis, histologic grade (P<0.01) and history of fibroadenoma (P<0.01) were independent prognostic factors for LR. No difference existed in the recurrence rate of BPT treated with different surgical procedures (P=0.397), whereas a higher recurrence rate was found in VABS and LE subgroups than in WLE and mastectomy subgroups for borderline/malignant tumors (P<0.01). Conclusions: No association found between surgical modalities and LR rate for BPT. We suggested a "wait-and-watch" policy for patients with unexpected benign subtypes, instead of unnecessary re-excision. In addition, VABS or LE can be treated for BPT with small mass, whereas WLE or even mastectomy should be conducted for borderline/malignant PTs with large mass.

FHL1 interacts with oestrogen receptors and regulates breast cancer cell growth.

Four and a half LIM protein 1 (FHL1) belongs to the Lin-1, Isl-1 and Mec-3 (LIM)-only protein family and plays important roles in muscle growth and carcinogenesis. However, the biological function of FHL1 remains largely unknown. Here, we show that FHL1 physically and functionally interacted with oestrogen receptors (ERs), which are involved in breast cancer development and progression. FHL1 bound specifically to the activation function-1 domain of ER. Physical interaction of FHL1 and ER is required for FHL1 repression of oestrogen-responsive gene transcription. FHL1 affected recruitment of ER to an oestrogen-responsive promoter and ER binding to an oestrogen-responsive element. Overexpression of FHL1 in breast cancer cells decreased expression of oestrogen-responsive proteins, whereas knockdown of endogenous FHL1 with FHL1 small interfering RNA increased the expression of these proteins. Further analysis of 46 breast cancer samples showed that FHL1 expression negatively associated with oestrogen-responsive gene expression in breast cancer cells. FHL1 inhibited anchorage-dependent and -independent breast cancer cell growth. These results suggest that FHL1 may play an important role in ER signalling as well as breast cancer cell growth regulation.

Advancement of prognostic models in breast cancer: a narrative review.

OBJECTIVE: To provide a reference for clinical work and guide the decision-making of healthcare providers and end-users, we systematically reviewed the development, validation and classification of classical prognostic models for breast cancer. BACKGROUND: Patients suffering from breast cancer have different prognosis for its high heterogeneity. Accurate prognosis prediction and risk stratification for breast cancer are crucial for individualized treatment. There is a lack of systematic summary of breast cancer prognostic models. METHODS: We conducted a PubMed search with keywords "breast neoplasm", "prognostic model", "recurrence" and "metastasis", and screened the retrieved publications at three levels: title, abstract and full text. We identified the articles presented the development and/or validation of models based on clinicopathological factors, genomics, and machine learning (ML) methods to predict survival and/or benefits of adjuvant therapy in female breast cancer patients. CONCLUSIONS: Combining prognostic-related variables with long-term clinical outcomes, researchers have developed a series of prognostic models based on clinicopathological parameters, genomic assays, and medical figures. The discrimination, calibration, overall performance, and clinical usefulness were validated by internal and/or external verifications. Clinicopathological models integrated the clinical parameters, including tumor size, histological grade, lymph node status, hormone receptor status to provide prognostic information for patients and doctors. Gene-expression assays deeply revealed the molecular heterogeneity of breast cancer, some of which have been cited by AJCC and National Comprehensive Cancer Network (NCCN) guidelines. In addition, the models based on the ML methods provided more detailed information for prognosis prediction by increasing the data dimension. Combined models incorporating clinical variables and genomics information are still required to be developed as the focus of further researches.

Pulmonary sarcoidosis: from clinical features to pathology- narrative review.

Sarcoidosis is a multisystem disease with unknown causes. The prevalence of sarcoidosis that occurs worldwide is highly variable. It is pathologically characterized by the formation of non-necrotizing epithelioid cell granuloma, mainly affecting the respiratory tract and involving extrapulmonary organs including the skin, heart, extrathoracic lymph nodes, central nerves and eyes. A correct diagnosis of sarcoidosis depends on the clinical symptoms, imaging observations, and characteristic histopathological findings. This study aims to review the recent contributions of pulmonary sarcoidosis. It is based on a search of a published article and review on pulmonary sarcoidosis. PubMed, Embase and CNKI were searched for latest developments from 1977. The most common clinical symptoms of sarcoidosis include dry cough, dyspnea, and chest discomfort. The imaging manifestations of sarcoidosis can be divided into typical and atypical findings. Lymphadenopathy is a typical imaging manifestation of sarcoidosis. Sarcoidosis is also a highly variable multisystem disease with an unpredictable clinical course. Clinically encountered cases cover a wide range from asymptomatic patients with incidental findings in radiographic images to chronic progressive diseases. Corticosteroids are the most widely recommended as the first-line treatment for symptomatic or organ-threatening disease in sarcoidosis, but they are associated with substantial toxic effects. Meanwhile, for sarcoidosis, the follow-up is also an important part of the diagnosis and treatment. Pulmonary sarcoidosis needs further recognition. In this paper, the clinical features, imaging observations, pathology, and treatment modalities for pulmonary sarcoidosis are presented and discussed vis-à-vis the current dilemma in diagnosis and therapy.

PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer.

Breast cancer is one of the most common life-threatening cancers, mainly because of its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood. Here, we demonstrated that lncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion, as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decreased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified that MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer. Overall, the results demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK/NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggesting that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.

Inverted-T pattern reduction mammoplasty in bilateral breast ptosis: cosmetic and oncological outcomes.

BACKGROUND: Breast ptosis is directly caused by Cooper's ligament laxity, with the decline of nipple areola complex (NAC) and mammary parenchyma. Breast cancer with ptosis is always a knotty problem that can hardly be repaired by classic breast conservation surgery (BCS) ending up with a pleasing appearance. We analyzed our 12 years' experience of performing inverted-T pattern techniques to treat bilateral breast ptosis, with or without breast cancer. METHODS: One hundred forty-eight breasts in 74 patients undergoing inverted-T pattern reduction mammoplasty were included in this study. Information about patients' clinical and surgical characteristics, complications, NAC sensitivity, cosmetic and oncological outcomes were collected and retrospectively analyzed. RESULTS: In the cohort of 57 patients with pure breast ptosis, the mean body mass index (BMI) was 25.2 kg/m2, and the mean weight of resected tissue from the left and right breast reductions were 744.9 and 756.7 g. In the cohort of 17 patients diagnosed as breast cancer with ptosis, the mean BMI was 25.1 kg/m2, and the mean weight of resected tissue were 504.1 g for left and 535.6 g for right side. The majority of repairs were performed for tumors located in the upper outer (58.8%), mostly with inferior or superomedial pedicles (90%). All the upper inner tumors were repaired with inferior pedicles. Minor complications such as seroma (8.1%), NAC epidermolysis (8.1%), delayed wound healing (4.1%) were detected postoperatively. Partial NAC necrosis occurred in one patient (1.4%). 82.4% of all the patients rated "very satisfied" or "satisfied" as the final cosmetic outcomes. NAC sensitivity was "very high" and "high" in 82.4% patients. No local occurrence, distant metastasis and mortality occurred in tumor patients. CONCLUSIONS: The inverted-T pattern reduction mammoplasty is a reliable technique to treat bilateral breast ptosis with a low complication rate. For cases with breast cancer, this technique can achieve both satisfying cosmetic outcomes and oncological safety.

Comparative healing of swine skin following incisions with different surgical devices.

BACKGROUND: Electrosurgical technology is widely used in surgical dissection and hemostasis, but the generated heat creates thermal injury to adjacent tissues and delays wound healing. The plasma blade (PB) applies pulsed radiofrequency (RF) to generate electrical plasma along the edge of a thin, flat, insulated electrode, minimizing collateral tissue damage. This study aimed to evaluate wound healing in swine skin following incision with a new surgical system that applies low-temperature plasma (NTS-100), a foreign PB, conventional electrosurgery (ES), and a scalpel blade. METHODS: In vitro porcine skin and an in vivo porcine skin model were used in this study. Full-thickness skin incisions 3 cm in length were made on the dorsum of each animal for each of the 5 surgical procedures at 0, 21, 28, 35, and 42 days. The timing of the surgical procedures allowed for wound-healing data points at 1, 2, 3, and 6 weeks accordingly. Local operating temperature and blood loss were quantified. Wounds were harvested at designated time points, tested for wound tensile strength, and examined histologically for scar formation and tissue damage. RESULTS: Local operating temperature was reduced significantly with NTS-100 (cut mode 83.12±23.55 °C; coagulation mode 90.07±10.6 °C) compared with PB (cut mode 94.46±11.48 °C; coagulation mode 100.23±6.58 °C, P<0.05) and ES (cut mode 208.99±34.33 °C, P<0.01; coagulation mode 233.37±28.69 °C, P<0.01) in vitro. Acute thermal damage from NTS-100 was significantly less than ES incisions (cut mode: 247.345±42.274 versus 495.295±103.525 µm, P<0.01; coagulation mode: 351.419±127.948 versus 584.516±31.708 µm, P<0.05). Bleeding, histological scoring of injury, and wound strength were equivalent for the NTS-100 and PB incisions. CONCLUSIONS: The local operating temperature of NTS-100 was lower than PB, and NTS-100 had similarly reliable safety and efficacy.

[Study on diagnostic accuracy of ultrasound-guided core needle breast biopsy].

OBJECTIVE: to evaluate the diagnostic accuracy of ultrasound-guided core needle biopsy of breast tumors. METHODS: six hundred and sixty-seven cases of core needle biopsy of breast encountered during the period from January, 2004 to June, 2007 were retrieved from the archival file and retrospectively reviewed. The core needle biopsy diagnoses were correlated with the histologic findings of the subsequent surgical excision specimens. The discrepancies were further analyzed. RESULTS: three hundred and eighty-two patients had core needle biopsy diagnosis followed by local excision, breast conservation surgery or mastectomy. Two hundred and eighty-one cases were confirmed to have malignancy in the surgical specimens. Review of the corresponding core needle biopsies showed 4 false-negative cases, no false-positive cases, 28 cases with underestimation and 2 cases with overestimation. The false-negative rate was 1.4% (4/281). The rate of underestimation for ductal carcinoma-in-situ was 6/11. The diagnostic accuracy of core needle biopsy was 94.7% (266/281). CONCLUSION: in order to improve the diagnostic accuracy of core needle biopsy of breast tumors, recognition of the limitation of the procedure, application of immunohistochemistry and awareness of potentially rare entities are important.

Glutathione ethyl ester supplementation prevents airway hyper-responsiveness in mice.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of asthma. Glutathione (GSH) is considered to be one of the most important antioxidants. Our study systematically investigated the effect of the GSH alternative, glutathione ethyl ester (GSH-EE), on airway hyper-responsiveness (AHR) in mice. METHODS: Sixty-three male specific pathogen-free mice were used. Asthma was induced using a single dose of ovalbumin (OVA). The normal group (n=15) received vehicle only [Al(OH)3 in saline]. Then, 48 mice were divided into two groups, including a control group who received sodium phosphate buffer (pH =7.4), and the GSH-EE group who received 0.1% GSH-EE. AHR was measured 2, 6, and 12 hours after exposure to nebulized OVA (0.01%). The animals were then sacrificed, and lung tissue and the bronchi-alveolar lavage fluid (BALF) were harvested. Factors involved in the antioxidant response to asthma were then measured in these tissues, including thiol content (from GSH and protein), γ-glutamylcysteine synthetase (γ-GCS) activity and expression, and nuclear factor-erythroid-2-related factor (Nrf2) expression. RESULTS: The GSH-EE group showed a significant attenuation of AHR (P<0.01) 2 hours after OVA challenge, and significantly enhanced thiol contents by approximately 45% (P<0.05) at 2 and 6 hours after the last OVA challenge, compared to the control group. γ-GCS activity was also higher in the GSH-EE group compared to the control group at different time points (P<0.01). γ-GCSh and Nrf2 protein expression increased in the GSH-EE group and the control group compared with the normal group, but there was no statistically significant difference (P>0.05) between the GSH-EE group and the control group. CONCLUSIONS: GSH-EE supplementation can prevent AHR in asthmatic mice during the early stages. It may function by serving as a precursor for GSH biosynthesis and by protecting sulfhydryl groups from oxidation.

Clinical features, prognosis, and influencing factors of contralateral prophylactic mastectomy in 58 patients with breast cancer.

BACKGROUND: The past two decades have witnessed the increasing application of contralateral prophylactic mastectomy (CPM) for women with breast cancer in the western countries. Over 30% of young patients choose to underwent CPM up to 2015. However, the adoption rate of CPM has not shown a remarkably increasing in Asian countries. In China, only a few centers have introduced CPM, and no relevant literature has been published. In this study, we look forward to identify the clinical features and prognostic factors of women who underwent CPM in our hospital, to inform decision-making processes for both doctors and patients. METHODS: The clinical data of 58 eligible patients were retrospectively analyzed. Intergroup comparisons were based on independent samples t-test and chi square test. The 5-year disease-free survival (DFS) and overall survival (OS) were obtained by using life tables, and factors affecting the survivals were analyzed by using the Kaplan-Meier method. RESULTS: The mean age of these women was 40.14±11.17 years, with 30 patients (51.7%) being ≤40 years; 13 patients (22.4%) had a family history of breast cancer; and 49 (69.0%) had known risk factors for breast cancer. The median follow-up period was 66.77 months, the 5-year OS was 89% and the 5-year DFS was 74%. The average age of onset was 41.53 (±10.964) in the disease-free survival group and 34.18 (±10.4) years in the recurrence/metastasis group, and t-test revealed a significant difference in the average age between these two groups (P=0.049). Chi-square test showed that the disease progression rate significantly differed among the different age subgroups and among subjects with different body mass index (BMI) (all P≤0.05). Moreover, surgical procedure, family history of breast cancer, and some other factors showed no significant correlation with disease progression (all P>0.05). Kaplan-Meier survival analysis and log rank test further confirmed the above findings. CONCLUSIONS: The majority of patients who choose CPM are young and with known risk factors for breast cancer. Part of the young patients (≤40 years of age) are at a higher risk of disease progression.

Snail promotes the generation of vascular endothelium by breast cancer cells.

A further understanding of tumor angiogenesis is urgently needed due to the limited therapeutic efficacy of anti-angiogenesis agents. However, the origin of endothelial cells (EC) in tumors remains widely elusive and controversial. Snail has been thoroughly elucidated as a master regulator of the epithelial-mesenchymal transition (EMT), but its role in endothelium generation is not yet established. In this study, we reported a new and unexpected function of Snail in endothelium generation by breast cancer cells. We showed that high Snail-expressing breast cancer cells isolated from patients showed more endothelium generated from these cells. Expression of Snail was positively correlated with endothelial markers in breast cancer patients. The ectopic expression of Snail induced endothelial marker expression, tube formation and DiI-AcLDL uptake of breast cancer cells in vitro, and enhanced tumor growth and microvessel density in vivo. Snail-mediated endothelium generation depended on VEGF and Sox2. Mechanistically, Snail promoted the expression of VEGF and Sox2 through recruiting the p300 activator complex to these promoters. We showed the dual function of Snail in tumor initiation and angiogenesis in vivo and in vitro through activation of Sox2 and VEGF, suggesting Snail may be an ideal target for cancer therapy.

The estrogen receptor-interacting protein HPIP increases estrogen-responsive gene expression through activation of MAPK and AKT.

Estrogen receptors (ERalpha and ERbeta) are estrogen-regulated transcription factors that play important roles in the development and progression of breast cancer. The biological function of ERs has been shown to be modulated by ER-interacting proteins. However, the ER-interacting proteins that not only activate MAPK and AKT, two important growth regulatory protein kinases, but also increase growth related estrogen-responsive gene expression remain unknown. Here, we report that hematopoietic PBX-interacting protein (HPIP) interacts both with ERalpha and with ERbeta, and increases ERalpha target gene expression through activation of MAPK and AKT and enhanced ERalpha phosphorylation. ERbeta inhibits ERalpha target gene expression, possibly by competition of ERbeta with ERalpha for binding to HPIP, and by a decrease in available ERalpha for HPIP binding through the interaction of ERbeta with ERalpha. Furthermore, HPIP increases breast cancer cell growth. These data suggest that HPIP may be an important regulator in ER signaling and that the relative ratio of ERbeta to ERalpha may be important for HPIP function.