Efficacy and Safety of Mitoxantrone Hydrochloride Injection for Tracing Axillary Sentinel Nodes in Breast Cancer: A Self-Controlled Clinical Trial.

Background: Mitoxantrone hydrochloride injection for tracing (MHI), a new strategy to identify lymph nodes, has not been tested for axillary node staging in breast cancer. This multicenter, self-controlled, non-inferiority trial aimed to evaluate MHI's efficacy and safety in sentinel lymph node biopsy (SLNB). Methods: The trial was conducted across seven hospitals from December 2019 to December 2020. Patients with early-stage breast cancer received MHI and technetium-99m (99mTc) during the surgery. Sentinel node detection rates were compared between MHI and 99mTc to evaluate non-inferiority and concordance. Non-inferiority was valid if the lower limit of the 95% CI of sentinel node relative detection rate difference was ≥-5%. Results: SLN relative detection rate of MHI was 97.31% (362/372). Of the SLNs, 79.69% (871/1093) were co-detected by both tracers. Of the patients, 4.13% (16/387) had adverse events and recovered during the follow-up. Conclusions: MHI is a lymphatic tracer with comparable efficacy to radionuclides and can be used alone or in combination with radioactive substances for SLNB. Clinical Trial Registration: http://www.chinadrugtrials.org.cn, CTR20192435.

Effects of Breast-Conserving Surgery Combined with Immediate Autologous Fat Grafting on Oncologic Safety, Satisfaction and Psychology in Patients with Breast Cancer: A Retrospective Cohort Study.

Purpose: Autologous fat grafting (AFG) is a technique that can improve the appearance of breasts in surgical patients. There are currently few studies on breast-conserving surgery (BCS) combined with immediate AFG, although we believe that it could achieve satisfactory effects. Therefore, the purpose of this study is to observe the effects of BCS combined with immediate AFG on oncologic safety, satisfaction and psychology of breast cancer patients. Patients and Methods: We retrospectively collected the data of 85 breast cancer patients from February 2018 to October 2018. After screening, 40 patients in AFG group (AG, BCS combined with immediate AFG) and 40 patients in control group (CG, BCS alone) were finally included in the study. The primary outcomes were the survival, tumor recurrence and metastasis, and BREAST-Q score of patients. The secondary outcomes were short and long-term complications, degree of depression and anxiety of patients. Results: A total of 80 patients were included in the analysis. There was no significant difference in the clinicopathological data between the two groups (P>0.05). The average follow-up time of the two groups was 40.58±2.630 and 40.28±2.679 months. In the analysis of oncologic safety, no patients died in AG and 1 patient died in CG. In addition, there was no significant difference between the two groups in terms of the overall recurrence rate and the distribution of recurrence types (P>0.05). As for satisfaction, the BREAST-Q score of AG was significantly higher than that of CG (57.85±4.833 vs 51.93±5.045, P<0.001). In the secondary outcomes, there was no short-term complication specified in the study; in the long-term complications, the incidence of calcification in AG was not significantly higher than that in CG (P=0.065). In the analysis of depression and anxiety, there was no significant difference between the two groups (P>0.05). Conclusion: BCS combined with immediate AFG can significantly improve patients' satisfaction without increasing the risk of death and tumor recurrence. However, it does not seem to play a role in improving the conditions of depression and anxiety.

Augmentation of antitumor function of tumor-infiltrating lymphocytes against triple-negative breast cancer by PD-1 blockade.

T-cell-based immunotherapy and immune checkpoint blockade have been successfully used to treat several human solid cancers. The present study attempted to investigate the feasibility and efficacy of the antitumor effect of adoptive cell therapy along with programmed cell death protein 1 (PD-1) inhibitor on triple-negative breast cancer (TNBC). Tumor infiltration lymphocytes (TILs) from TNBC mouse tumor tissues were isolated and expanded, and TILs for adoptive cell therapy (TILs-ACT) were applied in combination with a PD-1 inhibitor to the TNBC mouse model. The pre- and post-therapy antitumor efficacy, cytokine secretion, and pathological changes were assessed both in vitro and in vivo. We found that TILs exhibited higher IFN-γ and TNF-α secretion than conventional T cells. The TILs-ACT combined with PD-1 inhibitor promoted active T-cell infiltration into the tumor tissue and exerted a strong antitumor effect in an in vivo model. Additionally, the strategy could downregulate the expression of inhibitory marker PD-1 on TILs. In conclusion, PD-1 blockade regulated T-cell exhaustion that synergized with adoptive TIL transfer immunotherapy, leading to eradication of established TNBC tumors. These findings might be useful in developing a feasible and effective therapeutic approach for TNBC.

Long non-coding RNA H19 regulates proliferation and doxorubicin resistance in MCF-7 cells by targeting PARP1.

Chemoresistance is a major obstacle to effective breast cancer chemotherapy. However, the underlying molecular mechanisms remain unclear. The long noncoding RNA H19 (H19) is involved in various stages of tumorigenesis, however, its role in doxorubicin resistance remains unknown. The goal of this study was to evaluate the role of H19 in the development of doxorubicin-resistant breast cancer. Quantitative real-time PCR (qRT-PCR) analyzed H19 expression in chemotherapy-resistant and sensitive breast cancer tissues. Both knockdown and overexpression of H19 were used to assess the sensitivity to doxorubicin in breast cancer cells in vitro and in vivo. qRT-PCR and Western blot were used to explore the doxorubicin resistance mechanism of H19. We observed that the H19 expression was significantly upregulated in chemotherapy-resistant breast cancer tissues and doxorubicin-resistant breast cancer cell lines. Knockdown of H19 enhanced the sensitivity to doxorubicin both in vitro and in vivo. While H19 overexpression developed doxorubicin-resistant in breast cancer cells both in vitro and in vivo. Furthermore, it was revealed that H19 negatively regulated PARP1 expression in breast cancer cells following doxorubicin treatment. Knockdown of H19 sensitized breast cancer cells to doxorubicin by promoting PARP1 upregulation. H19 overexpression could recapitulate doxorubicin resistance by PARP1 downregulation. Our findings revealed that H19 plays a leading role in breast cancer chemoresistance development, mediated mainly through a H19-PARP1 pathway.

PIM1 is responsible for IL-6-induced breast cancer cell EMT and stemness via c-myc activation.

BACKGROUND: Interleukin-6 (IL-6) has been demonstrated to be a critical factor for breast cancer malignancy. However, the molecular mechanisms by which IL-6 induce breast cancer cells epithelial-mesenchymal-transition (EMT) and stemness remain elusive. METHODS: Breast cancer cell lines T47D and MCF7 were exposed to IL-6, the expression of PIM1 was examined by quantitative real-time PCR (qRT-PCR) and western blot. Luciferase reporter assay was used to determine the transcriptional modulation of PIM1 by IL-6 and STAT3 inhibitor. Transwell assay was used to detect the invading ability of breast cancer cells induced by IL-6 or PIM1. The expressions of EMT and stemness markers were determined by qRT-PCR. RESULTS: IL-6 promoted PIM1 expression in a dose- and time-dependent manner, and this induction could be abrogated by inhibiting STAT3 activation, subsequently suppressing the transcriptional level of PIM1. Moreover, we noticed that knocking down of PIM1 in cells which was exposed to IL-6 significantly impaired the invasion ability and the expression of EMT and stemness markers. On the contrary, overexpression of PIM1 promoted cell invasion and upregulated the expression of EMT and stemness markers. In addition, we demonstrated that c-myc, the cofactor of PIM1, involved in the pro-oncogenic roles of PIM1. Knocking down of c-myc attenuated the PIM1-induced cell EMT and stemness. CONCLUSION: This study proposed the upregulation of PIM1 by IL-6 contributed to breast cancer cell aggressiveness and targeting PIM1 or c-myc could be novel approaches for breast cancer treatment.

A novel IrNi@PdIr/C core-shell electrocatalyst with enhanced activity and durability for the hydrogen oxidation reaction in alkaline anion exchange membrane fuel cells.

Herein, a novel non-platinum core-shell catalyst, namely, IrNi@PdIr/C was prepared via a galvanic replacement reaction; it exhibits enhanced hydrogen oxidation activity and excellent stability under alkaline conditions. Electrochemical experiments demonstrated that the mass and specific activities at 50 mV of IrNi@PdIr/C are 2.1 and 2.2 times that of commercial Pt/C in 0.1 M KOH at 298 K, respectively. Moreover, accelerated degradation tests have shown that the electrochemically active surface area (ECSA) of IrNi@PdIr/C reduces by only 5.1%, which is almost 4 times less than that of commercial Pt/C and the mass activity at 50 mV of IrNi@PdIr/C after 2000 potential cycles is still 1.8 times higher than that of aged Pt/C. XRD and XPS analysis suggest that the enhanced HOR activity is attributed to the weakening of the hydrogen binding to the PdIr overlayers induced by the IrNi core. The better stability to potential cycling can be associated with the PdIr shell, which inhibits oxide formation. These results suggest that IrNi@PdIr/C is a promising non-platinum anode catalyst for alkaline anion exchange membrane fuel cells.

3D Pd/Co core-shell nanoneedle arrays as a high-performance cathode catalyst layer for AAEMFCs.

A novel cathode architecture using vertically aligned Co nanoneedle arrays as an ordered support for application in alkaline anion-exchange membrane fuel cells (AAEMFCs) has been developed. The Co nanoneedle arrays were directly grown on a stainless steel sheet via a hydrothermal reaction and then a Pd layer was deposited on the surface of the Co nanoneedle arrays using a vacuum sputter-deposition method to form Pd/Co nanoneedle arrays. After transferring the Pd/Co nanoneedle arrays to an AAEM, a cathode catalyst layer was formed. Without the use of an alkaline ionomer, the AAEMFC with the prepared cathode catalyst layer showed an enhanced performance with ultra-low Pd loading of down to 33.5 µg cm-2, which is much higher than the conventionally used cathode electrode with a Pt loading of 100 µg cm-2. This is the first report where three-dimensional Co nanoneedle arrays have been used as the cathode support in an AAEMFC, which is able to deliver a higher power density without an alkaline ionomer than that of conventional membrane electrode assembly (MEA).