Tumor Vasculature-Targeted Recombinant Mutated Human TNF-α Enhanced the Antitumor Activity of Doxorubicin by Increasing Tumor Vessel Permeability in Mouse Xenograft Models

Jiang, Changli; Niu, Junzhou; Li, Meng; Teng, Yi; Wang, Huixuan; Zhang, Yingqi

doi:10.1371/journal.pone.0087036

Cited by 12 publications

(8 citation statements)

References 24 publications

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“…In vivo anti-tumor efficacy of the conjugates was further enhanced in combination with irinotecan hydrochloride in mouse tumor xenograft models. As investigated by Jiang and coworkers, recombinant mutated human TNF-α (RGD-rmhTNF-α) showed ability to bind αvβ3 integrin in vitro, enhanced intratumoral uptake of Doxorubicin via increased permeability into tumor blood-vessels and synergistic anti-tumor efficacy with Doxorubicin in tumor xenograft models [51].…”

Section: Integrin-selective Drug/gene Delivery Platformsmentioning

confidence: 99%

Integrin-Mediated Delivery of Drugs and Nucleic Acids for Anti-Angiogenic Cancer Therapy: Current Landscape and Remaining Challenges

Majumder

2018

Bioengineering

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Angiogenesis, sprouting of new blood vessels from pre-existing vasculatures, plays a critical role in regulating tumor growth. Binding interactions between integrin, a heterodimeric transmembrane glycoprotein receptor, and its extracellular matrix (ECM) protein ligands govern the angiogenic potential of tumor endothelial cells. Integrin receptors are attractive targets in cancer therapy due to their overexpression on tumor endothelial cells, but not on quiescent blood vessels. These receptors are finding increasing applications in anti-angiogenic therapy via targeted delivery of chemotherapeutic drugs and nucleic acids to tumor vasculatures. The current article attempts to provide a retrospective account of the past developments, highlight important contemporary contributions and unresolved set-backs of this emerging field.

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Section: Integrin-selective Drug/gene Delivery Platformsmentioning

confidence: 99%

Integrin-Mediated Delivery of Drugs and Nucleic Acids for Anti-Angiogenic Cancer Therapy: Current Landscape and Remaining Challenges

Majumder

2018

Bioengineering

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“…20,21 It has also been reported that rmhTNF combined with traditional chemotherapeutic drugs can enhance the antitumor effect. 22,23…”

Section: Introductionmentioning

confidence: 99%

Hyperthermic intraperitoneal chemotherapy with recombinant mutant human TNF-α and raltitrexed in mice with colorectal-peritoneal carcinomatosis

Gong

Song

Wang

et al. 2020

Exp Biol Med (Maywood)

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Peritoneum is one of the most common metastatic sites of colorectal cancer (CRC). It has been reported that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) prolongs the lifespan of patients with peritoneal carcinomatosis of colorectal origin (CRC-PC), while the drugs used for HIPEC are limited. We investigated the application of recombinant mutant human tumor necrosis factor-α (rmhTNF) combined with raltitrexed in the HIPEC treatment in a mice model with CRC-PC. In vitro, we detected the cytotoxicity and apoptosis of human colorectal cancer cells by 3–(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, Western blot, and TdT-mediated dUTP Nick End Labeling (TUNEL) assay. In vivo, we established xenograft models of CRC-PC and assessed the antitumor effect by in vivo imaging, peritoneal cancer index scoring, and TUNEL assay. The results showed that the combination of rmhTNF and raltitrexed under hyperthermia with a temperature of 42°C inhibited the growth of colorectal cancer cells significantly in vitro, and after HIPEC treatments with rmhTNF and raltitrexed, peritoneal tumor growth was prohibited in vivo. Our findings about the efficacy of rmhTNF and raltitrexed used for HIPEC to treat CRC-PC will provide experimental data and basis for their potential clinical application. Impact statement Colorectal peritoneal carcinomatosis exhibits poor prognosis and presents a treatment challenge. At present, the main treatment is surgery, supplemented by hyperthermic intraperitoneal chemotherapy (HIPEC), but the drugs used for HIPEC are limited. Our study found that the combination of recombinant mutant human TNF-α (rmhTNF) and raltitrexed (RTX) under hyperthermia with a temperature of 42°C had antitumor effect both in vitro and vivo. The findings will provide experimental data and basis for the potential clinical application of rmhTNF and RTX, which might offer patients a new choice of therapeutic drugs.

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“…The therapeutic benefit from TNF-α can be ascribed to its anti-proliferative effects, and its ability to increase the penetration of chemotherapeutic agents into tumour tissues (17). An increasing body of evidence suggests that recombinant mutated human TNF (rmhTNF) acts synergistically with traditional chemotherapeutic drugs to exert enhanced antitumor effects (18). Recently, rmhTNF has been administered to patients with non-small cell lung cancer, non-Hodgkin lymphoma, or malignant pleura and ascites, when other therapies failed (19).…”

Section: Introductionmentioning

confidence: 99%

Effect of p53β on human gastric cancer cells treated with recombinant mutated human TNF and cisplatin

Yuan

Zhang

et al. 2017

Molecular Medicine Reports

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The present study aimed to investigate the role of tumour protein 53 isoform b (p53β) on human gastric cancer (GC) cell lines treated with recombinant mutated human tumour necrosis factor (rmhTNF) and cisplatin. The Cell Counting Kit‑8 assay was used to assess growth in the GC cell lines MKN45 and SGC7901, following treatment with rmhTNF in the presence or absence of cisplatin. Levels of p53β and bcl‑2 apoptosis regulator (bcl‑2) mRNA were assessed using reverse transcription‑polymerase chain reaction. The results demonstrated that growth was significantly inhibited by either cisplatin or rmhTNF treatments alone in MKN45 cells, and combination treatment with cisplatin and rmhTNF had a synergistic effect on growth inhibition of MKN45 cells. Notably, these observations were not evident in SGC7901 cells, where a mutant form of p53 is present. Treatment of MKN45 cells with rmhTNF did not affect bcl‑2 or p53β mRNA expression levels. However, treatment of MKN45 cells with cisplatin induced upregulation of p53β and downregulation of bcl-2 mRNA expression levels, and these effects were enhanced by combination treatment with rmhTNF. Pearson correlation analysis revealed a negative correlation between the expression of p53β and bcl‑2 mRNA, and a negative correlation between bcl-2 mRNA expression and the inhibition of cell growth. In conclusion, the inhibitory effect of cisplatin on the growth of MKN45 GC cells was enhanced by rmhTNF via unknown mechanisms that involved p53β, indicating that p53β may be an appropriate therapeutic target for the treatment of GC.

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Tumor Vasculature-Targeted Recombinant Mutated Human TNF-α Enhanced the Antitumor Activity of Doxorubicin by Increasing Tumor Vessel Permeability in Mouse Xenograft Models

Cited by 12 publications

References 24 publications

Integrin-Mediated Delivery of Drugs and Nucleic Acids for Anti-Angiogenic Cancer Therapy: Current Landscape and Remaining Challenges

Integrin-Mediated Delivery of Drugs and Nucleic Acids for Anti-Angiogenic Cancer Therapy: Current Landscape and Remaining Challenges

Hyperthermic intraperitoneal chemotherapy with recombinant mutant human TNF-α and raltitrexed in mice with colorectal-peritoneal carcinomatosis

Effect of p53β on human gastric cancer cells treated with recombinant mutated human TNF and cisplatin

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