Targeted axillary dissection after neoadjuvant chemotherapy for highly selective patients with initial cN1 breast cancer: A single-center prospective trial.

BACKGROUND: Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging). METHODS: This prospective trial included patients with initial pre-NAC cT1-3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated. RESULTS: A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30). CONCLUSIONS: In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%. REGISTRATION: chictr.org.cn , ChiCTR2100049093.

Resolving heterogeneity in schizophrenia, bipolar I disorder, and attention-deficit/hyperactivity disorder through individualized structural covariance network analysis.

Disruptions in large-scale brain connectivity are hypothesized to contribute to psychiatric disorders, including schizophrenia, bipolar I disorder, and attention-deficit/hyperactivity disorder. However, high inter-individual variation among patients with psychiatric disorders hinders achievement of unified findings. To this end, we adopted a newly proposed method to resolve heterogeneity of differential structural covariance network in schizophrenia, bipolar I disorder, and attention-deficit/hyperactivity disorder. This method could infer individualized structural covariance aberrance by assessing the deviation from healthy controls. T1-weighted anatomical images of 114 patients with psychiatric disorders (schizophrenia: n = 37; bipolar I disorder: n = 37; attention-deficit/hyperactivity disorder: n = 37) and 110 healthy controls were analyzed to obtain individualized differential structural covariance network. Patients exhibited tremendous heterogeneity in profiles of individualized differential structural covariance network. Despite notable heterogeneity, patients with the same disorder shared altered edges at network level. Moreover, individualized differential structural covariance network uncovered two distinct psychiatric subtypes with opposite differences in structural covariance edges, that were otherwise obscured when patients were merged, compared with healthy controls. These results provide new insights into heterogeneity and have implications for the nosology in psychiatric disorders.

Neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin in early triple-negative breast cancer: a single-arm phase II trial.

Immunotherapy combined with chemotherapy has been demonstrated to be effective in early triple-negative breast cancer (TNBC). In this single-arm, phase II study with Simon's two-stage design, we investigated the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy in patients with early TNBC (NCT04213898). Eligible female patients aged 18 years or older with histologically confirmed treatment-naïve early TNBC were treated with camrelizumab (200 mg, on day 1), nab-paclitaxel (125 mg/m2, on days 1, 8, and 15), and epirubicin (75 mg/m2, on day 1) every three weeks for six cycles. The primary end point was the pathological complete response; secondary endpoints included safety, objective response rate, and long-term survival outcomes of event-free survival, disease-free survival, and distant disease-free survival. A total of 39 patients were enrolled between January 2020 and October 2021. Twenty-five patients achieved a pathological complete response (64.1%, 95%CI: 47.2, 78.8). The objective response rate was 89.7% (95%CI: 74.8, 96.7), including 35 patients with partial responses. Treatment-related adverse events of grade 3 or 4 occurred in 30 (76.9%) patients. In conclusion, the trial meets the prespecified endpoints showing promising efficacy and manageable safety of neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin chemotherapy in female patients with early TNBC. Long-term survival outcomes are still pending.

A Nomogram for Identifying HR+/Her2- Breast Cancer Patients with Positive Sentinel Lymph Nodes and Omitted Axillary Lymph Node Dissection Who Need Abemaciclib Therapy.

BACKGROUND The efficacy of abemaciclib in high-risk patients with early-stage HR+/Her2- breast cancer has been verified by MonarchE. However, accurately determining the number of axillary lymph node (ALN) metastases remains challenging. The Z0011 trial changed the axillary management strategy, eliminating the need for axillary lymph node dissection (ALND) in patients with 1-2 sentinel lymph node (SLN) metastases. Therefore, further exploration is needed to identify patients who could benefit from abemaciclib therapy. MATERIAL AND METHODS This retrospective study included cT1-2N0M0 HR+/Her2- patients with 1-2 positive SLNs who underwent ALND. Clinicopathological data were collected, and logistic regression analyses identified independent predictors for ≥4 positive ALNs. A predictive nomogram was developed, and discrimination and calibration were evaluated using the C-index and calibration curve. Clinical efficacy was assessed using decision curve analysis (DCA). RESULTS We enrolled 444 patients, with 77 (17.3%) having ≥4 positive ALNs. Independent predictors for ≥4 positive ALNs included abnormal ALN on ultrasound, mammographic calcifications, T stage, and the number of positive SLNs. The nomogram demonstrated an AUC of 0.777 (95% CI: 0.735-0.815, P<0.001), and internal validation showed good calibration and discrimination (C-index, 0.802; 95% CI: 0.779-0.824). DCA revealed a positive net benefit for risk levels ranging from 5% to 54%. CONCLUSIONS This nomogram is a convenient and reliable tool to predict the risk of ≥4 positive ALNs in HR+/Her2- patients. It aids in protocol selection by identifying SLN-positive patients who may benefit from abemaciclib therapy without ALND.

Optimal surgical procedure for treating early-stage adenoid cystic carcinoma of the breast.

To explore the superiority of breast conservation surgery (BCS) to mastectomy in treating early-stage adenoid cystic carcinoma of the breast (BACC). Patients with surgically treated stage I/II BACC were enrolled between 2000 and 2019 in the SEER database; they were divided into the BCS and mastectomy groups. Overall survival (OS) and disease-specific survival (DSS) were compared between the two groups, and Cox hazard regression models were used to determine the independent predictors. Of the 583 patients in the study, 386 were included in the BCS group. The 10-year OS rates for the BCS and mastectomy groups were 78% (95% CI: 74-82%) and 76% (95% CI: 70-82%), respectively, but the difference was not statistically significant (p = 0.968). The 10-year DSS rates for the BCS and mastectomy groups were 95% (95% CI: 93-97%) and 89% (95% CI: 85-93%), respectively, and the difference was statistically significant (p = 0.002). Pathological examination of regional lymph nodes and adjuvant treatment were not associated with improved OS or DSS, but age, disease grade, and lymph node metastasis were independent prognostic factors. For stage I/II BACC, BCS can achieve more satisfactory 10-year OS and DSS than mastectomy.

Neoadjuvant Efficacy of Three Targeted Therapy Strategies for HER2-Positive Breast Cancer Based on the Same Chemotherapy Regimen.

(1) Background: The objective of our study was to provide evidence for choosing the optimal neoadjuvant therapy strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Three neoadjuvant targeted therapy strategies (H + Py, trastuzumab plus pyrotinib; H, trastuzumab; HP, trastuzumab plus pertuzumab) based on the same chemotherapy regimen (TC, docetaxel and carboplatin) were included in the present study; (2) Methods: We retrospectively analyzed patients with HER2-positive breast cancer who were treated with neoadjuvant TCH + Py, TCH or TCHP, followed by surgery. The outcome was the pathological complete response (pCR) rate; (3) Results: In total, 545 patients were enrolled. The pCR rate was 55.6% (35/63) in the TCH + Py cohort, 32.7% (93/284) in the TCH cohort, and 56.6% (112/198) in the TCHP cohort. The multivariate analysis showed that patients who received TCH had less possibility to achieve pCR than those who received TCH + Py (odds ratio (OR) = 0.334, 95% confidence interval (CI): 0.181−0.619, p < 0.001), while patients who received TCHP had comparable possibility to those who received TCH + Py (OR = 1.043, 95%CI: 0.554−1.964, p = 0.896); (4) Conclusions: TCH + Py provides a better pCR rate compared with TCH, and a comparable pCR rate with TCHP among patients with HER2-positive breast cancer in the neoadjuvant setting. The present study supports a novel potential treatment option for these patients. Further studies need to be explored in the future.

Pathological response and predictive role of tumour-infiltrating lymphocytes in HER2-positive early breast cancer treated with neoadjuvant pyrotinib plus trastuzumab and chemotherapy (Panphila): a multicentre phase 2 trial.

PURPOSE: Panphila evaluated pyrotinib plus trastuzumab, docetaxel and carboplatin as neoadjuvant therapy for early breast cancer (BC), and investigated the predictive role of immune cell subpopulations. PATIENTS AND METHODS: In this multicentre phase 2 study, patients with human epidermal growth factor receptor 2-positive, stage T2-3N0-3M0 BC received pyrotinib 400 mg once daily plus docetaxel (75 mg/m2, day 1), carboplatin (6 mg/mL/min, day 1) and trastuzumab (8 mg/kg loading dose and 6 mg/kg maintenance dose, day 1) for 6 cycles of 21 days each. Simon's 2-stage design was adopted. The primary end-point was pathological complete response (pCR, ypT0/is ypN0) rate. Tumour-infiltrating lymphocytes (TILs) were assessed by haematoxylin and eosin staining and multiplex immunohistochemistry. RESULTS: In the modified intention-to-treat population (n = 69), 38 patients (55.1%) achieved pCR. In the safety population (n = 74), the most common grade ≥3 adverse events were diarrhoea (43.2%), anaemia (37.8%), vomiting (16.2%) and platelet count decrease (10.8%). No treatment-related deaths occurred. Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by stromal (s)-CD20+, s-CD8+ and s-CD4+ TILs. Unsupervised hierarchical clustering of stromal immune markers identified a group of patients characterised by high s-CD20+, s-CD8+, s-CD4+ and s-FOXP3+ immune cells infiltration, which was independently associated with pCR. CONCLUSION: Neoadjuvant pyrotinib plus trastuzumab-based chemotherapy exhibits promising efficacy and manageable toxicity in patients with human epidermal growth factor receptor 2-positive early BC, and thus phase 3 trials are warranted. Our findings also contribute to understanding the potential role of the immune microenvironment in response to neoadjuvant pyrotinib-based therapy.

HBX suppresses PTEN to promote the malignant progression of hepatocellular carcinoma through mi-R155 activation.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common and fatal tumors in the world, ranking third in cancer-related mortality. Chronic HBV infection is one of the major risk factors for hepatocellular carcinoma in China, Korea, and Sub-Saharan Africa. The HBx protein encoded by the X gene of HBV is a broadly regulated protein involved in transcriptional activation, epigenetics, apoptosis, DNA repair, and other regulatory processes. This study aimed to investigate the mechanism of HBx regulation of miR-155 and PTEN (Phosphatase and tensin homolog deleted on chromosome ten) in HBV-HCC. METHODS: Exosomal miR-155 quantity was analyzed by sampling serum exosomes of patients with hepatocellular carcinoma and normal subjects. The analysis was divided into different subgroups according to HBV positivity or negativity. At the cellular level, the biological roles of HBX, microRNA-155 and PTEN on hepatocellular carcinoma cells and their regulatory relationships with each other were verified. RESULTS: MicroRNA-155 and PTEN expression in HBV-positive HCC liver cancer tissues were negatively correlated, and HBX and miR-155 expression were positively correlated; microRNA-155 could target and inhibit PTEN expression, thereby promoting hepatocellular carcinoma cell activity, inhibiting apoptosis, and promoting invasion and migration; HBX could upregulate microRNA-155 thereby inhibit PTEN to promote malignant transformation of hepatocellular carcinoma. CONCLUSIONS: HBX could promote malignant transformation of hepatocellular carcinoma cells by upregulating microRNA-155 expression and thereby inhibiting the PTEN/PI3K-AKT pathway. Blocking miR-155 expression could attenuate the proliferation-promoting and invasive effects of HBX.

In situ removal of cadmium by short-distance migration under the action of a low-voltage electric field and granular activated carbon.

Cd pollution in soil is a global environmental issue of great concern. The secondary release and low removal rate of Cd are obstacles to the use of adsorption techniques. To develop a sustainable and effective remediation technique, low-voltage direct current (DC) and granular activated carbon (GAC) were applied for in situ Cd removal. The results showed that a low-voltage gradient was more favourable than a high-voltage gradient for Cd removal. A voltage gradient of 0.2 V cm-1 acted as a driving force for Cd migration while limiting the side effects caused by DC. As an auxiliary enhancement measure, polarity exchange was effective in maintaining uniform distributions of soil moisture and temperature as well as a stable pH while improving Cd removal by weakening inhibition caused by OH- generated at the cathodes. The average removal rates of total and bioavailable Cd were 61.05% and 76.96%, respectively. The potential mobility of Cd in soil was assessed by the mobility factor (MF). The MF was lowered from 42.66% to 8.96%, indicating that the risks of Cd mobility were reduced to low levels. The energy consumption and utilization efficiency of the method were 5.65 KWh m-3 and 11.25, respectively. The energy utilization efficiency was significantly higher than the efficiencies of other methods that use DC to improve Cd removal. The results suggested that the in situ removal of Cd by low-voltage DC and GAC was efficient and avoided the secondary release of Cd.

Effect of the HER-2/CEP17 ratio in IHC 2+/FISH-amplified breast cancer on pathological complete response to neoadjuvant pertuzumab and trastuzumab treatment-a retrospective cohort study.

Background: Human epidermal growth factor receptor-2 (HER-2) protein expression level could serve as a predictor of pathological complete response (pCR) to neoadjuvant trastuzumab-containing regimens. The aim of the present study was to evaluate whether pCR to neoadjuvant trastuzumab and pertuzumab treatment is dependent on the level of the HER-2/CEP17 (chromosome enumeration probe 17) ratio in immunohistochemistry (IHC) 2+/fluorescence in situ hybridization (FISH)-amplified breast cancer. Methods: Patients with primary IHC 2+/FISH-amplified breast cancer who underwent neoadjuvant anti-HER-2 dual-targeted therapies were retrospectively included between January 1, 2020 and May 30, 2021. The primary predictive variable was HER-2/CEP17 ratio, and the primary outcome variable was pCR. Other variables consisted of age, menopausal status, tumor-node-metastasis (TNM) stage, estrogen receptor (ER), progesterone receptor (PgR), and Ki-67. Association between clinicopathologic variables and pCR was evaluated using the chi-square test and logistic regression analysis. Results: The median age of the patients was 51.78 years (25-67 years), and 50.7% of the patients were in the premenopausal stage. The clinical stage at diagnosis was Stage III in 38 patients (55.1%). Of all patients, 40.6% patients were estrogen receptor positive, and 75.4% patients had a Ki-67 index of ≥30%. The overall pCR (ypN0/isypN0) rate was 31.9%. Patients with HER-2/CEP17 ratio ≥6.0 had a pCR rate of 55.0%, it was statistically higher than 22.4% in patients with HER-2/CEP17 ratio <6.0. Logistic regression analysis confirmed the independent association between HER-2/CEP17 ratio and pCR (P=0.020, OR: 5.203, 95% CI: 1.302-20.783). Conclusions: A HER-2/CEP17 ratio ≥6.0 might be related to more achievement of pCR in the neoadjuvant anti-HER-2 dual-targeted therapies. Further studies are needed to validate the finding.

Establishment and Verification of a Predictive Model for Node Pathological Complete Response After Neoadjuvant Chemotherapy for Initial Node Positive Early Breast Cancer.

OBJECTIVE: Axillary node status after neoadjuvant chemotherapy (NCT) in early breast cancer patients influences the axillary surgical staging procedure. This study was conducted for the identification of the likelihood of patients being node pathological complete response (pCR) post NCT. We aimed to recognize patients most likely to benefit from sentinel lymph node biopsy (SLNB) following NCT and to reduce the risk of missed detection of positive lymph nodes through the construction and validation of a clinical preoperative scoring prediction model. METHODS: The existing data (from March 2010 to December 2018) of the Chinese Society of Clinical Oncology Breast Cancer Database (CSCO-BC) was used to evaluate the independent related factors of node pCR after NCT by Binary Logistic Regression analysis. A predictive model was established according to the score of considerable factors to identify ypN0. Model performance was confirmed in a cohort of NCT patients treated between January 2019 and December 2019 in Henan Cancer Hospital, and model discrimination was evaluated via assessing the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: Multivariate regression analysis showed that the node stage before chemotherapy, the expression level of Ki-67, biologic subtype, and breast pCR were all independent related factors of ypN0 after chemotherapy. According to the transformation and summation of odds ratio (OR) values of each variable, the scoring system model was constructed with a total score of 1-5. The AUC for the ROC curves was 0.715 and 0.770 for the training and the validation set accordingly. CONCLUSIONS: A model was established and verified for predicting ypN0 after chemotherapy in newly diagnosed cN+ patients and the model had good accuracy and efficacy. The underlined effective model can suggest axillary surgical planning, and reduce the risk of missing positive lymph nodes by SLNB after NCT. It has great value for identifying initial cN+ patients who are more appropriate for SLNB post-chemotherapy.

Establishing a prediction model of axillary nodal burden based on the combination of CT and ultrasound findings and the clinicopathological features in patients with early-stage breast cancer.

BACKGROUND: Axillary lymph node (ALN) management in early-stage breast cancer (ESBC) patients has become less invasive during the past decades. Here, we tried to explore whether high nodal burden (HNB) in ESBC patients could be predicted preoperatively, so as to avoid unnecessary sentinel lymph node biopsy (SLNB). METHODS: The clinicopathological and imaging data of patients with early invasive breast cancer (cT1-2N0M0) were analyzed retrospectively. Univariate and multivariate analyses were performed for the risk factors of axillary HNB in ESBC patients, and a risk prediction model of HNB was established. RESULTS: HNB was identified in 105 (8.0%) of 1,300 ESBC patients. Multivariate analysis showed that estrogen receptors (ER) status, human epidermal growth factor receptor 2 (HER2) status, number of abnormal lymph nodes (LNs) on computed tomography (CT), and axillary score on ultrasound (US) were the risk factors of HNB (all P<0.05). The area under the receiver operating characteristic (ROC) curve in the prediction model was 0.914, with the sensitivity being 85.7% and the specificity being 82.4%. The calibration curve showed that the prediction model had good performance. CONCLUSIONS: As a valuable tool for predicting HNB in ESBC patients, this newly established model helps clinicians to make reasonable axillary surgery decisions and thus avoid unnecessary SLNB.

Exosomal microRNA-155 as a biomarker for hepatic fibrosis diagnosis and progression.

BACKGROUND: Pathological examination of liver biopsies remains the gold standard for evaluating the stage of hepatic fibrosis, which are a number of disadvantages associated with biopsy. The aim of the present study was to investigate the potential of exosomal microRNA (miR)-155 as a non-invasive biomarker for the diagnosis and progression of hepatic fibrosis. METHODS: Exosomal miR-155 quantity was analyzed by sampling serum exosomes of patients with hepatic fibrosis and a hepatic fibrosis rat model. A total of 94 patients were divided into three groups based on Child-Pugh rating. Additionally, 30 patients with primary liver fibrosis who underwent liver transplantation were divided into the low miR-155 expression group and the high expression group; 56 rats were divided into 7 groups (n=8, 0, 2, 4, 6, 8, 10, and 12 weeks). Rats in every group were intravenously injected with CCl4 (3% vol/vol in olive oil; 0.3 mL/100 g body weight) twice weekly to produce different degrees of liver necrosis and liver fibrosis. RESULTS: Exosomal miR-155 was found to be closely associated with the progression of cirrhosis and clinical prognostic indicators of cirrhosis. Exosomal miR-155 gradually increased with the severity of hepatic necrosis and fibrosis. CONCLUSIONS: The findings of the present study indicate that exosomal miR-155 can act as a non-invasive biomarker for the diagnosis and progression of hepatic fibrosis.

Simultaneous delivery of anti-miRNA and docetaxel with supramolecular self-assembled "chitosome" for improving chemosensitivity of triple negative breast cancer cells.

At present, treating of triple negative breast cancer (TNBC) mainly depends on chemotherapy with more toxic side effects, but the effect is limited and it is highly prone to drug resistance. Gene therapy using anti-microRNAs maybe one of alternative therapeutic strategies. Due to the poor cell permeability and significant in vivo decomposition rate of anti-microRNAs, which limits their clinical application, we developed a core-shell supramolecular nanovector of "chitosome" that were self-assembled from the synthetic amphiphilic chitosan derivatives. The constructed chitosomes could co-load hydrophilic anti-miR-21 and hydrophobic docetaxel (DTX) into one combo nanocarrier with entrapment efficiency of more than 80%, as well as spherical morphology and average particle size of 90 nm. In comparison with the naked ones, anti-miR-21 encapsulated with chitosomes showed significantly increased cellular transfection and stability against degradation by nuclease in serum. Compared with DTX or anti-miR-21 formulations used alone, the co-delivery of the two drugs with the combo chitosome obtained improved chemosensitivity of TNBC cells to DTX treatment through their synergistic mechanisms. Taken together, the developed chitosome could be a promising candidate for simultaneous delivery of insoluble chemotherapeutic drugs and gene agents for TNBC therapy. Graphical abstract.

Comparison between surgery plus radiotherapy and radiotherapy alone in treating breast cancer patients with ipsilateral supraclavicular lymph node metastasis.

BACKGROUND: Ipsilateral supraclavicular lymph node metastasis (ISLM) with breast cancer patients has always been a hard problem for breast surgery. It is generally believed that radiotherapy can benefit the survival of patients, but whether local surgical resection is needed or not is controversial. The study aims to compare the efficacy between supraclavicular lymph node (SLN) dissection combined with radiotherapy and radiotherapy alone in the treatment of breast cancer with ISLM. METHODS: A retrospective analysis was performed using 122 cases of breast cancer with ISLM but without distant metastasis. Among them, 14 cases were eliminated due to insufficient data. The 108 remaining cases were divided into 2 groups based on different treatment proposals for metastatic SLNs. The groups were dissection plus radiotherapy (surgery group), and simple radiotherapy (radiotherapy group). RESULTS: For the 108 patients, the overall 5-year disease-free survival (DFS) and overall survival (OS) rates were 30.6% and 67.8%, respectively. In the surgery group, distant metastases occurred in 41 patients, and the 5-year DFS was 34.3%; in the radiotherapy group, 18 patients had distant metastases, and the 5-year DFS was 26.1%; the difference was not statistically significant (P>0.05). In the surgery group, 11 patients died, and the 5-year OS rate was 67.9%; in the radiotherapy group, 6 patients died, and the 5-year OS rate was 67.5%; the difference was not statistically significant (P>0.05). CONCLUSIONS: The dissection of SLN combined with radiotherapy and radiotherapy alone had similar effects on the survival rates in breast cancer patients with ISLM. The local control in the surgery group was better than that in the radiotherapy group. The status of estrogen receptors (ER) and the number of axillary lymph node metastases were independent influencing factors of DFS. The ER status is an independent factor affecting the OS rate of patients.

Natural deep eutectic solvent supported targeted solid-liquid polymer carrier for breast cancer therapy.

Solid-liquid nanocarriers (SLNs) are at the front of the rapidly emerging field of medicinal applications with a potential role in the delivery of bioactive agents. Here, we report a new SLN of natural deep eutectic solvent (NADES) and biotin-conjugated lysine-polyethylene glycol copolymer. The SLN system was analyzed for its functional groups, thermal stability, crystalline nature, particle size, and surface morphology through the instrumental analysis of FT-IR, TGA, XRD, DLS, SEM, and TEM. Encapsulation of PTX (paclitaxel) and 7-HC (7-hydroxycoumarin) with the SLN was carried out by dialysis, and UV-visible spectra evidenced the drug loading capacity and higher encapsulation efficiency obtained. The enhanced anticancer potential of PTX- and 7-HC-loaded SLN was assessed in vitro, and the system reduces the cell viability of MDA-MB-231 cells. The PTX- and 7-HC-loaded SLN system was investigated in a breast cancer-induced rat model via in vivo studies. It shows decreased lysosomal enzymes and increased levels of caspase to cure breast tumors. It very well may be reasoned that the designed PTX- and 7-HC-loaded SLN system has strong anticancer properties and exhibits potential for delivery of drug molecules in cancer treatment.

Long non-coding RNA LINC00968 reduces cell proliferation and migration and angiogenesis in breast cancer through up-regulation of PROX1 by reducing hsa-miR-423-5p.

Background: Breast cancer (BC) is a common invasive malignancy in women with unclear etiology. A recent study suggested that long non-coding RNA (lncRNA), LINC00968 had a tumor-promoting effect in cancer. However, the role of LINC00968 in BC remains unclear. Therefore, we conducted the present study to determine the effect of LINC00968 in BC and its underlying mechanism. Methods: The expression of LINC00968 and hsa-miR-423-5p in BC tissues and cells was determined using reverse transcription quantitative polymerase chain reaction and western blot analysis. Dual luciferase reporter, RNA pull-down and RNA immunoprecipitation assays were used to determine the relationship among LINC00968, PROX1 and hsa-miR-423-5p. Gain- and loss-function approaches were utilized to examine the effects of LINC00968, PROX1 and hsa-miR-423-5p on cell proliferation, migration, tube formation in vitro; and tumor growth and angiogenesis in vivo. Results: LINC00968 expression reduced while hsa-miR-423-5p increased in BC tissues relative to adjacent normal tissues. Overexpression of LINC00968 was observed to inhibit BC cell proliferation, migration and tube formation abilities in vitro as well as tumor growth in vivo through inhibition of hsa-miR-423-5p. And hsa-miR-423-5p mediated BC cellular functions and tumor growth through down-regulating PROX1. LINC00968 was identified as a competing endogenous RNA to upregulate PROX1 by downregulating hsa-miR-423-5p. More importantly, it was found that LINC00968 increased PROX1 expression in vivo in a concentration-dependent manner. Conclusion: Taken together, this study suggests that LINC00968 inhibits the progression of BC through impeding hsa-miR-423-5p-mediated PROX1 inhibition. LINC00968 may be a potential therapeutic target for BC therapy that warrants further studies.

LncRNA SNHG7 contributes to tumorigenesis and progression in breast cancer by interacting with miR-34a through EMT initiation and the Notch-1 pathway.

The long non-coding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) has been reported to be upregulated and contribute to carcinogenesis, progression and poor prognosis of many cancers. However, expression and function of SNHG7 in breast cancer remain unclear. Herein, we found that SNHG7 was significantly up-regulated in breast cancer tissues and cell lines. SNHG7 knockdown significantly inhibited MCF-7 cell proliferation and invasion, while SNHG7 overexpression dramatically promoted T47D cell proliferation and invasion. Xenograft experiments in vivo showed that SNHG7 knockdown significantly inhibited tumor growth in mice. In terms of mechanism, miR-34a was confirmed to be the target of SNHG7, and SNHG7 could sponge miR-34a to inhibit the expression of miR-34a. In vivo and in vitro experiments both showed that SNHG7 targeted miR-34a and promoted epithelial-to-mesenchymal transition (EMT) initiation and the Notch-1 pathway in breast cancer. In conclusion, SNHG7 promoted breast cancer tumorigenesis and progression by sponging miR-34a through EMT initiation and the Notch-1 pathway. These findings contribute to a better understanding of breast cancer pathogenesis and further provide the theoretical fundamental basis for treatment.

High-concentration glucose enhances invasion in invasive ductal breast carcinoma by promoting Glut1/MMP2/MMP9 axis expression.

Type 2 diabetes mellitus (T2DM) has been considered to be a risk factor for numerous human cancers. Hyperglycemia is one of the most direct internal environmental changes for patients with T2DM. Increasing evidence reveals that a high concentration of glucose can promote tumor progression, while its role for migration and invasion of invasive ductal breast carcinoma (IDBC) cells remains unclear. In the present study, it was demonstrated that IDBC patients with T2DM suffered an increased tumor size and more frequent lymphatic and distant metastasis compared with those without T2DM (P<0.05). MCF-7 breast carcinoma cells, which were cultured in a high glucose concentration medium (25.00 mM), exhibited increased invasion (P<0.05). In addition, the expression of glucose transporters (Gluts), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in IDBC tissues with T2DM was significantly higher compared to those without T2DM. Downregulation of glucose transporter 1 (Glut1) by small interfering RNA may markedly suppress MCF-7 cell invasion as well as the expression of MMP2 and MMP9. These results suggest that T2DM can affect the malignant features of tumors in IDBC. The high glucose concentration in the tumor microenvironment may enhance IDBC invasion via upregulating Glut1/MMP2/MMP9 axis expression.

Relationship between five GWAS-identified single nucleotide polymorphisms and female breast cancer in the Chinese Han population.

With the development of genome-wide association study (GWAS), an increasing number of genetic variables have been confirmed to be associated with breast cancer. Furthermore, an increasing number of studies from Asian populations are becoming available. Few GWAS loci have been replicated in the Chinese Han population. In a case-control study of breast cancer in the Henan Tumor Hospital (253 cases/339 controls), we evaluated five SNPs from GWAS of populations of European or Asian ancestry. In order to evaluate the contribution of genetic factors to population differences in breast cancer subtypes, all cases are defined by estrogen (ER), progesterone (PR) receptor, Human epidermal growth factor receptor - 2 (HER2), and Ki67 status. Different genotypes of rs3803662 (TOX3)/ (TNRC9)) in the case group and the control group are statistically significant (P = 0.044), but the ones of rs10069690 (TERT), rs2046210 (6q25.1), rs2981582 (EGFR2), and rs889312 (MAP3K1) have no significant statistical differences with breast cancer (P = 0.772, 0.308, 0.376, 0.468). The allelic frequencies of rs3803662 between the case group and the control group differ in recessive genetic models (odds ratio (OR) = 2.04, 95 % confidence interval (CI) 1.14-3.66) and in con-dominant inheritance models (OR = 2.17, 95 % CI 1.18-4.00). Compared with AA and GA, GG increased the risk of breast cancer (P = 0.017, 0.013). The genotype of rs2046210 (6q25.1), rs2981582 (EGFR2), rs889312 (MAP3K1), and rs3803662 (TOX3/TNRC9) has no statistical differences in different subtypes of breast cancer. Five common breast cancer susceptibility loci from GWAS are not strongly associated with breast cancer risk among the Han Chinese of the Henan province; only rs3803662 (TOX3/TNRC9) is confirmed to increase the risk of breast cancer. The different genotypes of five loci distribute equally in different subtypes of breast cancer.