Tissue factor-targeted lidamycin inhibits growth and metastasis of colon carcinoma

Zhang, Qing; Liu, Xiujun; Li, Caihong; Liao, Dongsheng; Ouyang, Zhi-Gang; Zheng, Junnian; Xu, Song

doi:10.3892/ol.2013.1437

Cited by 3 publications

(3 citation statements)

References 22 publications

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“…Circulating tumor and host‐derived tissue factor (TF) has been identified as an important link between cancer and thrombosis and TF expression has been reported in colon 26 cell lines . We therefore examined the contribution of circulating TF activity to our results and found that specifically blocking tissue factor in plasma from sham control, cachectic and non‐cachectic mice had no effect on thrombin generation under our conditions, suggesting the observed hypercoagulability was secondary to other factors.…”

Section: Discussionmentioning

confidence: 87%

Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin‐6 dependent

Reddel

Allen

Ehteda

et al. 2017

Journal of Thrombosis and Haemostasis

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Background Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer, which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. Objectives To assess if cancer cachexia altered the coagulation state and if this was attributable to tumor IL-6 production. Methods In male BALB/c*DBA2 (F1 hybrid) mice with a C26 tumor we used modified calibrated automated thrombogram and fibrin generation (based on overall hemostatic potential) assays to assess the functional coagulation state, and also examined fibrinogen, erythrocyte sedimentation rate (ESR), platelet count, tissue factor pathway inhibitor (TFPI) and hepatic expression of coagulation factors by microarray. C26 mice were compared with non-cachectic NC26, pair-fed and sham control mice. IL-6 expression in C26 cells was knocked down by lentiviral shRNA constructs. Results C26 mice with significant weight loss and highly elevated IL-6 had elevated thrombin generation, fibrinogen, ESR, platelets and TFPI compared with all control groups. Fibrin generation was elevated compared with pair-fed and sham controls but not compared with NC26 tumor mice. Hepatic expression of coagulation factors and fibrinolytic inhibitors was increased. Silencing IL-6 in the tumor significantly, but incompletely, attenuated the increased thrombin generation, fibrinogen and TFPI. Conclusions Cachectic C26 tumor-bearing mice are in a hypercoagulable state, which is partly attributable to IL-6 release by the tumor. The findings support the importance of the coagulation state in cancer cachexia and the clinical utility of anti-inflammatory interventions.

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Section: Discussionmentioning

confidence: 87%

Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin‐6 dependent

Reddel

Allen

Ehteda

et al. 2017

Journal of Thrombosis and Haemostasis

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“…In this study, we chose mlFVII as the target-binding domain of the TF-CAR. Because mFVII possesses equivalent affinity to mTF and hTF [ 23 , 24 ], the TF-CAR T cells could attack both hTF-expressing tumor cells and mTF-expressing normal tissues in our mouse models; therefore, this system can stimulate the behavior of TF-CAR T cells with hlFVII as the target vehicle in the human body to a certain extent. Our data showed that after 3 infusions of TF-CAR T cells, no obvious pathological changes were detected in the important organs of the mice, such as the heart, liver, spleen, lung and kidney (Figure 8C ).…”

Section: Discussionmentioning

confidence: 99%

“…Others and we have previously shown that the light chain of FVII retained the affinity of original FVII to its receptor TF [ 21 , 22 ]. The light chains of the human and mouse FVII-conjugated drugs (hlFVII-LDM, mlFVII-LDM) that we developed showed effective growth suppression of TF-positive human lung cancer and mouse colon cancer, respectively [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Chimeric antigen receptor-modified T Cells inhibit the growth and metastases of established tissue factor-positive tumors in NOG mice

Zhang

et al. 2016

Oncotarget

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Chimeric antigen receptor (CAR)-modified T cell (CAR T) is a promising therapeutic option for patients with cancer. Such an approach requires the identification of tumor-specific antigen targets that are expressed in solid tumors. We developed a new third-generation CAR directed against tissue factor (TF), a surface molecule overexpressed in some types of lung cancer, melanoma and other cancers. First, we demonstrated by immunohistochemistry that TF was overexpressed in squamous cell carcinoma and adenocarcinoma of non-small cell lung cancer (NSCLC) and melanoma using a human tissue microarray. In the presence of TF-positive cancer cells, the CAR-modified T cells (TF-CAR T) were highly activated and showed specific cytotoxicity to TF-positive cancer cells in vitro. In established s.c. xenograft and lung metastasis models, TF-CAR T cells could significantly suppress the growth of s.c. xenograft and metastasis of TF-positive cancer cells. Additionally, the safety evaluation of TF-CAR T cells in vivo showed that the treatment did not cause obvious toxicity in mice. Taken together, these findings indicate that TF-CAR T cells might be a novel potential therapeutic agent for the treatment of patients with TF-positive cancers.

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Tubeimoside I induces autophagy in HepG2 cells by activating the AMP‑activated protein kinase signaling pathway

et al. 2020

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Tubeimoside I (TBMS) is a natural compound with antitumor properties. However, the detailed mechanism underlying the function of TBMS in liver cancer has not been fully elucidated. In the present study, TBMS was shown to suppress cell proliferation and induce S phase cell cycle arrest in HepG2 cells. Furthermore, TBMS treatment induced autophagy, evidenced by autophagosome accumulation, and increased the mRNA expression of Beclin 1 and microtubule-associated protein 1 light chain 3 (LC3)-I. However, flow cytometry analysis demonstrated that TBMS exerted no effect on cell apoptosis. Moreover, TBMS increased the phosphorylation of AMP-activated protein kinase (AMPK) in a concentration-dependent manner, thereby activating the AMPK signaling pathway. A specific AMPK inhibitor, compound C (CC), caused markedly suppressed TBMS-induced accumulation of LC3-II. In addition, the mRNA expression of LC3-Ι and Beclin 1 was also suppressed in cells treated with TBMS and CC in combination. The results of the present study provide new insights into the role of TBMS in inducing autophagy and support the potential application of TBMS for liver cancer treatment in the clinical setting.

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Tissue factor-targeted lidamycin inhibits growth and metastasis of colon carcinoma

Cited by 3 publications

References 22 publications

Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin‐6 dependent

Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin‐6 dependent

Chimeric antigen receptor-modified T Cells inhibit the growth and metastases of established tissue factor-positive tumors in NOG mice

Tubeimoside I induces autophagy in HepG2 cells by activating the AMP‑activated protein kinase signaling pathway

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