Neoadjuvant pyrotinib plus nab-paclitaxel, doxorubicin, and cyclophosphamide for HER2-positive locally advanced breast cancer: a retrospective case-series study.

BACKGROUND: The anti-tumor activity of pyrotinib has been confirmed in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. This study investigated the effect of pyrotinib plus nab-paclitaxel, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with HER2-positive locally advanced breast cancer. METHODS: In this single-center retrospective study, female patients with HER2-positive locally advanced breast cancer received pyrotinib 320 mg orally once a day and the TAC regimen (nab-paclitaxel 260 mg/m2, liposomal doxorubicin 20 mg/m2, and cyclophosphamide 600 mg/m2) on day 1 of each 21-day cycle. Surgery was performed after 4-6 cycles of neoadjuvant therapy. The outcomes included total pathological complete response (tpCR, ypT0/Tis ypN0) rate, objective response rate (ORR) after neoadjuvant therapy, progression-free survival, overall survival, and the incidence of adverse events (AEs). RESULTS: Between March 2019 and January 2020, a total of 22 patients were included. The median age was 48 years (range, 32-60). The ORR was 100% after the completion of neoadjuvant therapy. Ten (45.5%) patients achieved tpCR, including four of ten (40.0%) patients with positive hormone receptor, and six of 12 (50.0%) patients with negative hormone receptor. As at December 2020, no disease recurrence, progression, or death occurred. All patients suffered AEs after neoadjuvant therapy, most of which were grade 1-2. Grade ≥3 AEs included diarrhea [4 (18.2%)], rash [2 (9.1%)], and hand-foot syndrome [1 (4.5%)]. CONCLUSIONS: Neoadjuvant pyrotinib combined with the TAC regimen showed promising clinical benefit in patients with HER2-positive locally advanced breast cancer, with an acceptable safety profile.

Ginsenoside Rh3 activates Nrf2 signaling and protects endometrial cells from oxygen and glucose deprivation-reoxygenation.

Oxygen and glucose deprivation (OGD)-reoxygenation (OGDR) induces oxidative injury to endometrial cells in vitro. We tested the potential effect of ginsenoside Rh3 (GRh3) in the process. Our results show that GRh3 activated Nrf2 signaling in T-HESC cells and primary murine endometrial cells. GRh3 induced Nrf2 Ser-40 phosphorylation and Keap1-Nrf2 disassociation, causing Nrf2 protein stabilization and nuclear translocation, which led to transcription and expression of antioxidant response element-dependent genes (HO1, NQO1 and GCLC). In T-HESC cells and primary murine endometrial cells, GRh3 potently attenuated OGDR-induced reactive oxygen species production, lipid peroxidation and mitochondrial depolarization, as well as cell viability reduction and necrosis. Activation of Nrf2 is required for GRh3-induced anti-OGDR actions in endometrial cells. Nrf2 inhibition, by Nrf2 shRNA, knockout (through CRISPR-Cas9-editing) or S40T mutation, abolished GRh3-induced endometrial cell protection against OGDR. Additionally, forced activation of Nrf2, by Keap1 knockout, mimicked and nullified GRh3-induced anti-OGDR actions in T-HESC cells. Together, we conclude that GRh3 protects endometrial cells from OGDR via activation of Nrf2 signaling.

[Effect of TAK1 gene silencing on the apoptosis of Kasumi-1 cells induced by arsenic trioxide].

OBJECTIVE: To study the effect of transforming growth factor-ß activated kinase-1 (TAK1) gene silencing on the proliferation and apoptosis of Kasumi-1 cells induced by arsenic trioxide (As2O3). METHODS: Acute myeloid leukemia with t(8;21) cell line Kasumi-1 cells were treated with As2O3 or in combination with TAK1 siRNA interference technology. The experiment was divided into four groups: Kasumi-1 cells without any treatment, TAK1 specific siRNA transfection alone, Kasumi-1 cells treated with different concentration of As2O3, TAK1siRNA transfection combined with As2O3. CCK-8 was used to detect the cell viability. The expression of phosphorylated c-Jun N-terminal kinase (P-JNK) was determined by Western Blot. Cell apoptosis and growth were examined by morphological and colony formation assay. RESULTS: After Kasumi-1 cells were treated with As2O3, the rate of cell inhibition was concentration-dependent, and the 50% inhibitory concentration was 3.5 µmol/L. The highest expression level of P-JNK appeared in 30 minutes after cells were treated with As2O3. The apoptosis rates of Kasumi-1 cells without any treatment, TAK1 siRNA interference alone group, As2O3 alone group and the combined group were (5.02 ± 1.13)%, (6.18 ± 0.28)%, (48.33 ± 2.70)% and (86.07 ± 2.21)%; colony formation rates were (73.83 ± 2.78)%, (76.03 ± 1.46)%, (55.07 ± 1.50)% and (22.20 ± 1.15)%; apoptosis rate of TAK1 siRNA group and the untreated group has no significant difference (P = 0.052); colony formation rate between TAk1 siRNA group and the untreated group has no significant difference (P = 0.179), but the difference in other groups was significant (P = 0.000). CONCLUSION: Silencing the expression of TAK1 can enhance the anti-proliferative and pro-apoptotic effect of As2O3 on Kasumi-1 cells, and its mechanism may be through the TAK1 downstream JNK signal pathway.

A monometallic tri-spin single-molecule magnet based on rare earth radicals.

A mononuclear tri-spin single-molecule magnet based on the rare earth radical [Tb(hfac)3(NITPhOEt)2] (NITPhOEt = 4'-ethoxy-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) has been synthesized, structurally characterized and the alternating current signals show a slow relaxation of magnetization and frequency-dependent signals.

Four new lanthanide-nitronyl nitroxide (Ln(III) = Pr(III), Sm(III), Eu(III), Tm(III)) complexes and a Tb(III) complex exhibiting single-molecule magnet behavior.

Five new complexes based on rare-earth-radical [Ln(hfac)(3)(NIT-5-Br-3py)](2) (Ln = Pr (1), Sm (2), Eu (3), Tb (4), Tm (5); hfac = hexafluoroacetylacetonate; NIT-5-Br-3py = 2-(4,4,5,5-tetramethyl-3-oxylimidazoline-1-oxide)-5-bromo-3-pyridine) have been synthesized and characterized by X-ray crystal diffraction. The single-crystal structures show that these complexes have similar structures, in which a NIT-5-Br-3py molecule acts as a bridging ligand linking two Ln(III) ions through the oxygen atom of the N-O group and nitrogen atom from the pyridine ring to form a four-spin system. Both static and dynamic magnetic properties were measured for complex 4, which exhibits single-molecule magnetism behavior.

[Advances in the study of tumor pH-responsive polymeric micelles for cancer drug targeting delivery].

This review presents the state of the art of pH-responsive polymeric micelles for cancer drug delivery. Solid tumors have a weakly acidic extracellular pH (pH < 7), and cancer cells have even more acidic pH in endosomes and lysosomes (pH 4-6). The pH-gradients in tumor can be explored for tumor targeting and drug release in cancer drug delivery by applying pH-responsive polymeric micelles. The pH-responsive polymeric micelles consist of a corona and a core, and are made of amphiphilic copolymers, in which there are pH-responsive polymeric blocks. Two types of pH-responsive polymers-protonizable polymers and acid-labile polymers have been mainly used to make pH-responsive micelles for drug delivery. The protonizable polymers are polybases or polyacids, and their water-soluble/insoluble or charge states undergo changes with the protonation or deprotonation stimulated by external acidity, while the acid-labile polymers change their physical properties by chemical reaction stimulated by the acidity. Polymeric micelles whose core or coronas respond to the tumor extracellular acidity can be explored for triggering the fast release of the carried drug, activating the targeting group and accelerating the endocytosis of drug-loaded polymeric micelles, and those whose core or coronas respond to the tumor lysosomal acidity can be used for facilitating their escape from the lysosomes and targeting the nucleus. Various in vivo and in vitro experiments demonstrated that pH-responsive polymeric micelles are effective for cellular targeting, internalization, fast drug release and nuclear localization, and hence enhancing the therapeutic efficacy and reducing the side effect of cancer chemical therapy.