Heterogeneous-Structure-Based AuNBs@TiO2 Nano-Photosensitizers for Computed Tomography Imaging Guided NIR-II Photodynamic Therapy and Cancer Metastatic Prevention.

Photodynamic therapy (PDT) is a minimally invasive cancer treatment that, despite its significant attention, faces limitations in penetration depth, which restrict its effectiveness. Herein, it is found that gold nanobipyramid (AuNBs) coated with TiO2 can form a core-shell heterogeneous structure (AuNBs@TiO2) with strong absorption at second near infrared (NIR-II) region. A substantial quantity of reactive oxygen species (ROS), including singlet oxygen (1O2), superoxide anion radicals, and hydroxyl radicals, can be rapidly generated when subjecting the AuNBs@TiO2 aqueous suspension to 1064 nm laser irradiation. The quantum yield for sensitization of 1O2 by AuNBs@TiO2 is 0.36 at 1064 nm light excitation. In addition, the Au element as high-Z atoms in the nanosystem can improve the ability of computed tomographic (CT) imaging. As compared to commercial iohexol, the AuNBs@TiO2 nanoparticle exhibits significantly better CT imaging effect, which can be used to guide PDT. In addition, the nano-photosensitizer shows a remarkable therapeutic effect against established solid tumors and prevents tumor metastasis and potentiates immune checkpoint blockade therapy. More importantly, here the great potentials of AuNBs@TiO2 are highlighted as a theranostic platform for CT-guided cancer photodynamic immunotherapy.

Quantitative characterization of tumor cell traction force on extracellular matrix by hydrogel microsphere stress sensor.

Cell traction force (CTF) is a kind of active force that is a cell senses external environment and actively applies to the contact matrix which is currently a representative stress in cell-extracellular matrix (ECM) interaction. Studying the distribution and variation of CTF during cell-ECM interaction help to explain the impact of physical factors on cell behaviors from the perspective of mechanobiology. However, most of the strategies of characterizing CTF are still limited by the measurement needs in three-dimensional (3D), quantitative characteristics and in vivo condition. Microsphere stress sensor (MSS) as a new type of technology is capable of realizing the quantitative characterization of CTF in 3D and in vivo. Herein, we employed microfluidic platform to design and fabricate MSS which possesses adjustable fluorescent performances, physical properties, and size ranges for better applicable to different cells (3T3, A549). Focusing on the common tumor cells behaviors (adhesion, spreading, and migration) in the process of metastasis, we chose SH-SY5Y as the representative research object in this work. We calculated CTF with the profile and distribution to demonstrate that the normal and shear stress can determined different cell behaviors. Additionally, CTF can also regulate cell adhesion, spreading, and migration in different cell states. Based on this method, the quantitative characterization of CFT of health and disease cells can be achieved, which further help to study and explore the potential mechanism of cell-ECM interaction.

Amide-sulfamide modulators as effective anti-tumor metastatic agents targeting CXCR4/CXCL12 axis.

Breast cancer is the most frequently diagnosed malignancy and the second common cause of death in women worldwide. High mortality in breast cancer is frequently associated with metastatic progression rather than the primary tumor itself. It has been recently identified that the CXCR4/CXCL12 axis plays a pivotal role in breast cancer metastasis, especially in directing metastatic cancer cells to CXCL12-riched organs and tissues. Herein, taking the amide-sulfamide as the lead structure, the second-round structural modifications to the sulfamide structure were performed to obtain more active CXCR4 modulators against tumor metastasis. Both in vivo and in vitro experiments illustrated that compound IIIe possessed potent CXCR4 binding affinity, excellent anti-metastatic and anti-angiogenetic activity against breast cancer. More importantly, in a mouse breast cancer lung metastasis model, compound IIIe exerted a significant inhibitory effect on breast cancer metastasis. Taken together, all these positive results demonstrated that developing of CXCR4 modulators is a promising strategy to mediate breast cancer metastasis.

Research progress on the role of Ang/Tie axis in angiogenesis and metastasis / 药学学报

The tumor contains abundant new vessels, which are unevenly distributed, irregular, and branch-disordered. Angiopoietin (Ang) and tyrosine kinase receptor Tie mediate stable maturation of angiogenesis. Ang1 mainly plays a role in promoting vascular stabilization, and Ang2 is highly expressed in vessels, which makes the structure and function of vessels abnormal. Leaked vessels provide opportunities for invasion and metastasis of circulating tumor cells. Targeting the Ang/Tie axis to correct the abnormal state of vessels and promote its normalization, combined with chemotherapy drugs or immunotherapy, play a synergistic effect against tumors. This article summarizes the role of Ang/Tie axis in tumor angiogenesis and metastasis, and it aims to provide new ideas and strategies for clinical treatment of tumors.

Surgery for metastatic gastrointestinal stromal tumor: to whom and how to?

Although imatinib is a standard treatment for metastatic or recurrent gastrointestinal stromal tumors (GISTs), acquired c-kit mutations reportedly cause secondary resistance to imatinib. Sunitinib is a tyrosine kinase inhibitor (TKI) that can be used as second-line therapy in imatinib-resistant or -intolerant GISTs. For sunitinib-resistant or -intolerant GISTs, regorafenib is a standard third-line treatment. Although TKI therapies have revolutionized the treatment of recurrent or metastatic GISTs, they cannot cure GISTs. Therefore, in the era of TKIs, role of cytoreductive surgery for recurrent or metastatic GISTs has been discussed. Retrospective studies of treatment strategies with front-line surgery prior to imatinib have shown that initial cytoreduction confers no benefit in cases of advanced or recurrent GIST, and administering imatinib is the principle treatment. Most retrospective studies report cytoreductive surgery to be feasible in patients with metastatic GIST whose disease is stable or responsive to imatinib. Cytoreductive surgery may be indicated in limited disease progression refractory to imatinib when complete resection is possible, but case selection is critical. Cytoreductive surgery for metastatic GIST treated with sunitinib seems less feasible because of high rates of incomplete resections and complications. The role of cytoreductive surgery for metastatic GISTs would be difficult to establish in a prospective study; individualized treatments need to be carefully designed based on c-kit and platelet-derived growth factor receptor alpha (PDGFRA) mutations and other factors.

Study of signaling pathway related tophosphatase of regenerating liver 3 / 医学研究生学报

PRL-3, belonging to the family of protein tyrosine phosphatase, has been found to be high expressed in colorectal cancer, gastric cancer, ovarian cancer and melanoma.It also has been reported that PRL-3 plays an important role in the progression of tumor.With the distinction of PRL-3 in tumor progression, especially in the metastatic tumor, there are more and more researches about the regulating mechanism of PRL-3.This paper reviews the development of signaling pathway of PRL-3.