Nifuroxazide prompts antitumor immune response of TCL-loaded DC in mice with orthotopically-implanted hepatocarcinoma

Zhao, Tiesuo; Jia, Hui‐Zhen; Qian, Cheng; Xiao, Yali; Li, Minming; Li, Chen; Feng, Yuchen; Feng, Zhiwei; Wang, Hui; Zheng, Junnian

doi:10.3892/or.2017.5629

Cited by 25 publications

(20 citation statements)

References 41 publications

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“…The current treatment of melanoma is based on surgery plus chemotherapy or radiation therapy; however, even dacarba-zine, the standard first-line treatment for melanoma, does not improve the overall survival benefit ( 2 ). Previous studies have reported that numerous Food and Drug Administration (FDA)-approved drugs may be useful as novel pharmacotherapies in the treatment of malignant tumours ( 3 – 6 ). Consequently, additional novel drugs need to be identified to suppress cancer cell growth, diversify options and enhance the effectiveness of antitumour therapy.…”

Section: Introductionmentioning

confidence: 99%

The enhanced antitumour response of pimozide combined with the IDO inhibitor L‑MT in melanoma

et al. 2018

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Melanoma is one of the most fatal and therapy-resistant types of cancer; therefore, identifying novel therapeutic candidates to improve patient survival is an ongoing effort. Previous studies have revealed that pimozide is not sufficient to treat melanoma; therefore, enhancing the treatment is necessary. Indoleamine 2, 3-dioxygenase (IDO) is an immunosuppressive, intracellular rate-limiting enzyme, which contributes to immune tolerance in various tumours, including melanoma, and inhibition of IDO may be considered a novel therapeutic strategy when combined with pimozide. The present study aimed to assess the antitumour activities of pimozide in vitro, and to investigate the effects of pimozide combined with L-methyl-tryptophan (L-MT) in vivo. For in vitro analyses, the B16 melanoma cell line was used. Cell cytotoxicity assay, cell viability assay, wound-healing assay and western blotting were conducted to analyse the effects of pimozide on B16 cells. Furthermore, B16 cell-bearing mice were established as the animal model. Haematoxylin and eosin staining, immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end-labelling staining, western blotting and flow cytometry were performed to determine the effects of monotherapy and pimozide and L-MT cotreatment on melanoma. The results demonstrated that pimozide exhibited potent antitumour activity via the regulation of proliferation, apoptosis and migration. Furthermore, the antitumour effects of pimozide were enhanced when combined with L-MT, not only via regulation of proliferation, apoptosis and migration, but also via immune modulation. Notably, pimozide may regulate tumour immunity through inhibiting the activities of signal transducer and activator of transcription (Stat)3 and Stat5. In conclusion, the present study proposed the use of pimozide in combination with the IDO inhibitor, L-MT, as a potential novel therapeutic strategy for the treatment of melanoma.

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Section: Introductionmentioning

confidence: 99%

The enhanced antitumour response of pimozide combined with the IDO inhibitor L‑MT in melanoma

et al. 2018

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“…In these activities, the blocking of the STAT3 pathways plays an important role. Nifuroxazide can be effective as prophylaxis or second-line therapy for aGvHD (4)(5)(6)(7)(8)(28)(29)(30). It can be assumed that this old drug will find a new application in medicine.…”

Section: Resultsmentioning

confidence: 99%

Safety of oral nifuroxazide – analysis of data from a spontaneous reporting system

Karłowicz-Bodalska¹,

Głowacka²,

Boszkiewicz³

et al. 2019

Acta Poloniae Pharmaceutica - Drug Research

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Nifuroxazide (4-hydroxy-benzoic acid; 2-[(5nitro-2-furanyl)methylene]hydrazide) is a chemotherapeutic agent belonging to the nitrofuran family. Indications for its use are acute and chronic bacterial diarrhea and other diseases with diarrhea (1). The drug has local antibacterial activity against some Gram-positive bacteria of the genus Staphylococcus and Gram-negative bacteria from the Enterobacteriaceae family: Yersinia spp., Escherichia spp., Enterobacter spp., Klebsiella spp. and Salmonella spp. It does not affect the bacteria Proteus vulgaris, Proteus mirabilis and Pseudomonas aeruginosa (1-3). Recently, attention has been paid to its antitumor potential in neuroblastoma, multiple myeloma, colorectal and breast cancer, efficacy in the treatment of graft-versus-host disease and nephroprotection in diabetes (4-10). The exact mechanism of action of nifuroxazide has not yet been identified. It probably has an inhibitory effect on dehydrogenase activity and protein synthesis in bacterial cells. Aldehyde dehydrogenase (ALDH) is responsible for the bioactivation of this prodrug. It has been found that nifuroxazide is a potent inhibitor of the Janus kinase 2 pathways and transcription factor 3 (JAK2/STAT3). It also has direct effects on oxidative stress and apoptosis (2, 4-6). Frequent self-administration of this drug by patients makes it necessary to pay attention to selfmedication, which in accordance with the guidelines of the World Health Organization is defined as ìusing medication by the consumer to treat signs/symptoms or minor health problems, recognized as such by themselvesî. In practice, this term also includes treatment by family members or friends, mainly, when the child is being treated (11). It should be responsible and safe, especially considering that diarrhea, in particular, acute diarrhea, is a serious problem of primary and hospital care. Itís serious complications, such as electrolyte disturbances, oligovolemic shock and even death, are dangerous especially for newborns, babies, small children and elderly people, due to their susceptibility to dehydration (12, 13). The fact that adverse effects inevitably accompany the desired therapeutic effects

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“…STAT3 inhibitors, including AZD9150 and TTI-101, have entered the clinical trial phase for HCC treatment (ClinicalTrials.gov identifier: NCT03195699 and NCT01839604, respectively). Several drugs, which were not initially applied for tumor treatment, have also been found to exert anticancer effects by blocking STAT3[58-60]. Thus, the identification of new STAT3-targeted inhibitors is still an important direction for drug development.…”

Section: Molecular Mechanisms Underlying Hccmentioning

confidence: 99%

Hepatocellular carcinoma: Mechanisms of progression and immunotherapy

Yu¹,

Han²,

Zhang³

2019

WJG

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Liver cancer is one of the most common malignancies, and various pathogenic factors can lead to its occurrence and development. Among all primary liver cancers, hepatocellular carcinoma (HCC) is the most common. With extensive studies, an increasing number of molecular mechanisms that promote HCC are being discovered. Surgical resection is still the most effective treatment for patients with early HCC. However, early detection and treatment are difficult for most HCC patients, and the postoperative recurrence rate is high, resulting in poor clinical prognosis of HCC. Although immunotherapy takes longer than conventional chemotherapy to produce therapeutic effects, it persists for longer. In recent years, the emergence of many new immunotherapies, such as immune checkpoint blockade and chimeric antigen receptor T cell therapies, has given new hope for the treatment of HCC.

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Nifuroxazide prompts antitumor immune response of TCL-loaded DC in mice with orthotopically-implanted hepatocarcinoma

Cited by 25 publications

References 41 publications

The enhanced antitumour response of pimozide combined with the IDO inhibitor L‑MT in melanoma

The enhanced antitumour response of pimozide combined with the IDO inhibitor L‑MT in melanoma

Safety of oral nifuroxazide – analysis of data from a spontaneous reporting system

Hepatocellular carcinoma: Mechanisms of progression and immunotherapy

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