A dual-catalytic nanoreactor for synergistic chemodynamic-starvation therapy toward tumor metastasis suppression

2021 ◽  
Author(s):  
Huiwen Zhang ◽  
Fei Lu ◽  
Wei Pan ◽  
Yegang Ge ◽  
Bingjie Cui ◽  
...  

Tumor metastasis is extremely deadly for cancer patients and developing effective treatments for deep metastatic tumors remains a major challenge. In this study, we demonstrated a dual-catalytic nanoreactor for tumor...

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e59412 ◽  
Author(s):  
Nuo Xu ◽  
Deshui Jia ◽  
Wenfeng Chen ◽  
Hao Wang ◽  
Fanglei Liu ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1730-1739 ◽  
Author(s):  
Youya Nakazawa ◽  
Shigeo Sato ◽  
Mikihiko Naito ◽  
Yukinari Kato ◽  
Kazuhiko Mishima ◽  
...  

Abstract CD9 has been reported to play a role in tumor metastasis suppression. However, it is not fully understood how CD9 affects the hematogenous spread of tumor cells. To clarify a new mechanism (or mechanisms), we generated HT1080 cells that had been transfected with a CD9-expressing plasmid. Ectopic expression of CD9 in HT1080 cells actually reduced their metastatic ability. CD9 expression reduced lung retention and platelet ag-gregation activity of the transfectants. Because HT1080 cells express the metastasis-promoting, platelet aggregation-inducing factor Aggrus/podoplanin on their surface, we examined the relationship between CD9 and Aggrus. We discovered that CD9 formed a complex with Aggrus via transmembrane domains 1 and 2 (TM1 and TM2) of CD9. Investigation of the interaction revealed that each CD9 and Aggrus interacted homophilically, and that they colocalized in low-density membrane fractions. Deleting TM1 and TM2 attenuated the ability of CD9 to interact homophilically or to localize in low-density membrane fractions. The expression of CD9–wild-type (WT), but not CD9 lacking TM1 and TM2, attenuated the platelet aggregation and metastasis induced by forced expression of Aggrus in CHO cells. Therefore, CD9 may act as a metastasis suppressor, at least in part, by neutralizing Aggrus-mediated platelet aggregation.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xi-Yang Tang ◽  
An-Ping Shi ◽  
Yan-Lu Xiong ◽  
Kai-Fu Zheng ◽  
Yu-Jian Liu ◽  
...  

This study highlights aspects of the latest clinical research conducted on the relationship between immune checkpoints and tumor metastasis. The overview of each immune checkpoint is divided into the following three sections: 1) structure and expression; 2) immune mechanism related to tumor metastasis; and 3) clinical research related to tumor metastasis. This review expands on the immunological mechanisms of 17 immune checkpoints, including TIM-3, CD47, and OX-40L, that mediate tumor metastasis; evidence shows that most of these immune checkpoints are expressed on the surface of T cells, which mainly exert immunomodulatory effects. Additionally, we have summarized the roles of these immune checkpoints in the diagnosis and treatment of metastatic tumors, as these checkpoints are considered common predictors of metastasis in various cancers such as prostate cancer, non-Hodgkin lymphoma, and melanoma. Moreover, certain immune checkpoints can be used in synergy with PD-1 and CTLA-4, along with the implementation of combination therapies such as LIGHT-VTR and anti-PD-1 antibodies. Presently, most monoclonal antibodies generated against immune checkpoints are under investigation as part of ongoing preclinical or clinical trials conducted to evaluate their efficacy and safety to establish a better combination treatment strategy; however, no significant progress has been made regarding monoclonal antibody targeting of CD28, VISTA, or VTCN1. The application of immune checkpoint inhibitors in early stage tumors to prevent tumor metastasis warrants further evidence; the immune-related adverse events should be considered before combination therapy. This review aims to elucidate the mechanisms of immune checkpoint and the clinical progress on their use in metastatic tumors reported over the last 5 years, which may provide insights into the development of novel therapeutic strategies that will assist with the utilization of various immune checkpoint inhibitors.


Author(s):  
A. A. Gryazov ◽  
M. I. Lisyany ◽  
A. B. Gryazov

Background. Studies carried out in recent decades have shown that immune cells are essential participants in the cancer process as well as cancerrelated inflammation. Focus has been increased on understanding the way how immune cells affect a tumor at different stages of the disease: early neoplastic transformation, clinically detected tumors, metastatic spread, and at surgery and radiotherapy stages. Purpose – assessing the status of the immune system in patients with brain tumors before radiation therapy and radiosurgery and comparing the features of immunity in metastatic and glial brain tumors. Materials and methods. The study presents the immunogram findings of 61 patients. Out of those: 18 patients with primary glial tumors and 23 patients with secondary metastatic tumors to the brain. The outcomes of 20 conditionally healthy non-cancer patients are presented as a control group. The age of patients is 24–75. All patients were histologically diagnosed with the tumor. Surgery was performed 1.0–3.0 years before the examination. Assessment of the immune system in patients with brain tumors was performed taking into account the cellular, humoral and phagocytic component of innate immunity. When assessing cellular immunity, the relative and absolute count of major lymphocyte subpopulations, such as CD3+ – general T-lymphocytes, CD4+ – T-lymphocytes-helpers, CD8+ – cytotoxic lymphocytes, CD16+ – natural killer lymphocytes, CD19+-B-lymphocytes, were calculated. Determining the humoral parameters included an assessment of quantitative values of IgG, IgM and IgA. Quantitative assessment of the phagocytic component of innate immunity included phagocytic activity of neutrophils (i. e. NBT test (Nitroblue Tetrazolium test), inducing (Zymosanum) and spontaneous neutrophil myeloperoxidase activity). Results. When comparing the immune parameters of the number of T- and B-subpopulations of lymphocytes in patients with primary malignant brain tumors and secondary metastatic tumors, no statistically significant difference has been detected between these params. Glioblastomas show higher levels of СD4+- and CD8+-lymphocytes in comparison with other tumour groups as well as higher levels of IgG and IgA than in other tumors, while IgM concentration is almost at the same level in three groups of patients. There is a tendency for reducing IgG and IgM level in the blood of patients with metastatic tumors. Both groups of cancer patients under study show inhibition of myeloperoxidase activity of neutrophils in the setting of maintaining the function of NBT cell activity. Conclusions. According to the findings obtained via studying immunological indicators of brain tumors, both metastatic and primary malignant glial ones, there are partial changes in various immune system components such as cellular, humoral and phagocytic activity. However, no statistically significant difference was detected between immune status indicators, that substantiates the need for further study of this issue. At the stage of preparation for radiation therapy, no significant changes in the immune system of the patients with brain tumors, that would make such treatment impossible and be consiered as one of contraindications, are observed.


1987 ◽  
Vol 57 (02) ◽  
pp. 140-143 ◽  
Author(s):  
Egbert de Jong ◽  
Eduard A R Knot ◽  
Dick Piket ◽  
Alfred H C Iburg ◽  
Dick C Rijken ◽  
...  

SummaryPlasminogen activator(PA) - tissue and urokinase type - and PA-inhibition in plasma were investigated in 52 consecutive cancer patients with a variety of tumors. At first patients were analyzed as one group. Secondly patients were subdivided into two groups, one with (n = 42) and one without (n = 10) metastasis. Our results show that tissue-type-PA antigen (t-PA-antigen) and PA-inhibition were both significantly increased irrespective of the presence or absence of tumor metastasis (p <0.001) compared to age matched healthy controls. In the group without metastasis a significantly decreased level of t-PA activity was found (p <0.001) but in the group with metastasis t-PA activity was normal. These data seem to reject the hypothesis that decreased plasma fibrinolytic activity is one of the prerequisites for tumor metastasis.


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