Tianjin Medical University

About: Tianjin Medical University is a education organization based out in Tianjin, China. It is known for research contribution in the topics: Cancer & Metastasis. The organization has 19345 authors who have published 13942 publications receiving 241709 citations. The organization is also known as: Tiānjīn Yīkē Dàxué.

Codelivery of Anti‐PD‐1 Antibody and Paclitaxel with Matrix Metalloproteinase and pH Dual‐Sensitive Micelles for Enhanced Tumor Chemoimmunotherapy

Abstract: Immune checkpoint blockade (ICB) is demonstrating great potential in cancer immunotherapy nowadays. Yet, the low response rate to ICB remains an urgent challenge for tumor immunotherapy. A pH and matrix metalloproteinase dual-sensitive micellar nanocarrier showing spatio-temporally controlled release of anti-PD-1 antibody (aPD-1) and paclitaxel (PTX) in solid tumors is prepared to realize synergistic cancer chemoimmunotherapy. Antitumor immunity can be activated by PTX-induced immunogenic cell death (ICD), while aPD-1 blocks the PD-1/PD-L1 axis to suppress the immune escape due to PTX-induced PD-L1 up-regulation, thus resulting in a synergistic antitumor chemoimmunotherapy. Through decoration with a sheddable polyethylene glycol (PEG) shell, the nanodrug may better accumulate in tumors to boost the synergistic antitumor treatment in a mouse melanoma model. The present study demonstrates a potent antitumor chemoimmunotherapy utilizing tumor microenvironment-sensitive micelles bearing a sheddable PEG layer to mediate site-specific sequential release of aPD-1 and PTX.

Micro RNA 100 sensitizes luminal A breast cancer cells to paclitaxel treatment in part by targeting mTOR

Abstract: Luminal A breast cancer usually responds to hormonal therapies but does not benefit from chemotherapies, including microtubule-targeted paclitaxel. MicroRNAs could play a role in mediating this differential response. In this study, we examined the role of micro RNA 100 (miR-100) in the sensitivity of breast cancer to paclitaxel treatment. We found that while miR-100 was downregulated in both human breast cancer primary tumors and cell lines, the degree of downregulation was greater in the luminal A subtype than in other subtypes. The IC50 of paclitaxel was much higher in luminal A than in basal-like breast cancer cell lines. Ectopic miR-100 expression in the MCF-7 luminal A cell line enhanced the effect of paclitaxel on cell cycle arrest, multinucleation, and apoptosis, while knockdown of miR-100 in the MDA-MB-231 basal-like line compromised these effects. Similarly, overexpression of miR-100 enhanced the effects of paclitaxel on tumorigenesis in MCF-7 cells. Rapamycin-mediated inhibition of the mammalian target of rapamycin (mTOR), a target of miR-100, also sensitized MCF-7 cells to paclitaxel. Gene set enrichment analysis showed that genes that are part of the known paclitaxel-sensitive signature had a significant expression correlation with miR-100 in breast cancer samples. In addition, patients with lower levels of miR-100 expression had worse overall survival. These results suggest that miR-100 plays a causal role in determining the sensitivity of breast cancers to paclitaxel treatment.

Prognostic value of chemotherapy-induced neutropenia in early-stage breast cancer

Abstract: Neutropenia is one of the most important dose-limiting toxicities and often the reason for dose reduction In this study we aimed to assess whether chemotherapy-induced neutropenia could be a marker of efficacy and associate with increased survival Data from a retrospective survey for early breast cancer patients in our hospital were reviewed Three hundred and thirty-five patients who had been treated with six cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF) were studied The association between chemotherapy-induced neutropenia and overall survival (OS) was assessed According to a multivariate Cox model with time-varying covariates, hazard ratios of death were 0434 (95% confidence interval (CI), 0298–0634; P < 0001) for patients with mild neutropenia, and 0640 (95% CI, 042–0975; P = 0038) for those with severe neutropenia Neutropenia occurring in early breast cancer patients is an independent predictor of increased survival These findings suggest that neutropenia in patients who receive chemotherapy is strongly associated with a better prognosis

The dual role of autophagy under hypoxia-involvement of interaction between autophagy and apoptosis.

Abstract: Hypoxia is one of severe cellular stress and it is well known to be associated with a worse outcome since a lack of oxygen accelerates the induction of apoptosis. Autophagy, an important and evolutionarily conserved mechanism for maintaining cellular homeostasis, is closely related to the apoptosis caused by hypoxia. Generally autophagy blocks the induction of apoptosis and inhibits the activation of apoptosis-associated caspase which could reduce cellular injury. However, in special cases, autophagy or autophagy-relevant proteins may help to induce apoptosis, which could aggravate cell damage under hypoxia condition. In addition, the activation of apoptosis-related proteins–caspase can also degrade autophagy-related proteins, such as Atg3, Atg4, Beclin1 protein, inhibiting autophagy. Although the relationship between autophagy and apoptosis has been known for rather complex for more than a decade, the underlying regulatory mechanisms have not been clearly understood. This short review discusses and summarizes the dual role of autophagy and the interaction and molecular regulatory mechanisms between autophagy and apoptosis under hypoxia.