Tissue Factor and Tissue Factor Pathway Inhibitor in Nasal Mucosa and Nasal Secretions of Chronic Rhinosinusitis with Nasal Polyp

Shimizu, Shino; Ogawa, Takao; Takezawa, Kumiko; Tojima, Ichiro; Kouzaki, Hideaki; Shimizu, Takeshi

doi:10.2500/ajra.2015.29.4183

Cited by 37 publications

(27 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among these proteins, the majority of coagulation pathway‐related proteins were overexpressed in the tissue of CRSwNP patients. This finding comports with multiple previous studies in the literature . In addition, our results demonstrate a downregulation of much of the fibrinolysis‐associated proteome.…”

Section: Discussionsupporting

confidence: 92%

“…Recently, the clustering of patients using endotypes, or distinct functional pathobiologic mechanisms, has gained popularity. Functional alterations in the coagulation system have been previously identified as potential etiopathologic agents in CRSwNP and could serve as biosignatures to help delineate patient endotype . Consequently, we sought to apply a novel proteomic approach to delve more deeply into the coagulation pathway derangements in CRSwNP and to simultaneously determine whether exosomal expression of these altered proteins could be used as a novel noninvasive method to understand the disease.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have described altered protein expression in nasal polyps relative to control mucosa . Interestingly, derangements in coagulation pathway proteins have featured prominently in many of these reports . Coagulation proteins circulate in the blood and are activated by a proteolytic cascade to generate active enzymes.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Highly multiplexed proteomic analysis reveals significant tissue and exosomal coagulation pathway derangement in chronic rhinosinusitis with nasal polyps

Müller

Nocera

Dillon

et al. 2018

Int Forum Allergy Rhinol

View full text Add to dashboard Cite

Our proteomic analysis confirmed that the coagulation pathway is highly significantly deranged within nasal polyp tissue. The correlation between tissue- and mucus-derived exosomal fibrinolysis and coagulation protein alterations were strong, inverse, and highly significant. This lends further support to the emerging concept of exosomal proteomic analysis as a method to study chronic sinonasal inflammation.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Highly multiplexed proteomic analysis reveals significant tissue and exosomal coagulation pathway derangement in chronic rhinosinusitis with nasal polyps

Müller

Nocera

Dillon

et al. 2018

Int Forum Allergy Rhinol

View full text Add to dashboard Cite

show abstract

“…Almost all epistaxis events were grade 1, and none required clinical intervention. Moreover, as TF is highly expressed in the nasal epithelium (31), this observation may reflect a local disruption of the nasal mucosa rather than an underlying treatment-induced coagulopathy. The incidence of other bleeding-related events was consistent with the expected incidence observed in patients with advanced cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer

Hong

Concin

Vergote

et al. 2020

Clinical Cancer Research

View full text Add to dashboard Cite

◥Purpose: Tissue factor (TF) is a potential target in cervical cancer, as it is frequently highly expressed and associated with poor prognosis. Tisotumab vedotin, a first-in-class investigational antibody-drug conjugate targeting TF, has demonstrated encouraging activity in solid tumors. Here we report data from the cervical cancer cohort of innovaTV 201 phase I/II study (NCT02001623).Patients and Methods: Patients with recurrent or metastatic cervical cancer received tisotumab vedotin 2.0 mg/kg every 3 weeks until progressive disease, unacceptable toxicity, or consent withdrawal. The primary objective was safety and tolerability. Secondary objectives included antitumor activity.Results: Of the 55 patients, 51% had received !2 prior lines of treatment in the recurrent or metastatic setting; 67% had prior bevacizumab þ doublet chemotherapy. Fifty-one percent of patients had squamous cell carcinoma. The most common grade 3/4 treatment-emergent adverse events (AEs) were anemia (11%), fatigue (9%), and vomiting (7%). No grade 5 treatment-related AEs occurred. Investigator-assessed confirmed objective response rate (ORR) was 24% [95% confidence interval (CI): 13%À37%]. Median duration of response (DOR) was 4.2 months (range: 1.0 þ À9.7); four patients responded for >8 months. The 6-month progression-free survival (PFS) rate was 29% (95% CI: 17%À43%). Independent review outcomes were comparable, with confirmed ORR of 22% (95% CI: 12%À35%), median DOR of 6.0 months (range: 1.0 þ À9.7), and 6-month PFS rate of 40% (95% CI: 24%À55%). Tissue factor expression was confirmed in most patients; no significant association with response was observed.Conclusions: Tisotumab vedotin demonstrated a manageable safety profile and encouraging antitumor activity in patients with previously treated recurrent or metastatic cervical cancer.Cervical cancer is a common cancer in women, with an estimated 570,000 new cases globally in 2018, and represents the third leading cause of cancer-related death in women worldwide (1). Approximately 15,500 and 61,000 new cases of cervical cancer were estimated in North America and in Europe in 2018, respectively, resulting in approximately 5,800 and 25,800 deaths (2). Recurrent or metastatic cervical cancer has a poor prognosis, with a 5-year survival rate of 17% (3). Bevacizumab and doublet chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) were adopted as first-line (1L) standard-ofcare therapy for recurrent or metastatic cervical cancer in the past 5 years (4-6). However, nearly all patients relapse after 1L treatment, and single-institution experiences indicate that the percentage of patients who receive a second-line (2L) therapy varies (30%-70%) as many patients die before receiving treatment (7,8).Available 2Lþ therapies for recurrent or metastatic cervical cancer are characterized by low response rates (5,6). Before adoption of bevacizumab plus doublet chemotherapy in 1L, therapies administered in the 2Lþ setting reported response rates in the range of 4.5% to 15%, with median s...

show abstract

“…Eosinophils were found to express TF, which initiates the extrinsic coagulation cascade and subsequent fibrin deposition . Binding of factor VIIa to TF on the surface of cells initiates the coagulation cascade by activating both factors IX and X, which in turn leads to thrombin generation and subsequent fibrin clot formation .…”

Section: Resultsmentioning

confidence: 99%

Increased expression of L‐plastin in nasal polyp of patients with nonsteroidal anti‐inflammatory drug‐exacerbated respiratory disease

Takabayashi

Tanaka

Susuki

et al. 2018

Allergy

View full text Add to dashboard Cite

Background: Most patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) suffer from recurrence of nasal polyps. However, little is known about the specific cellular and molecular mechanisms contributing to the pathogenesis of nasal polyp development in patients with NERD in particular, especially at baseline when cyclooxygenase 1 inhibitors are not present. The objectives of this study were to identify proteins involved in the pathogenesis of nasal polyps in patients with NERD. Methods:We collected nasal polyp tissue from patients with NERD and from patients with aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP).Protein profiles were analyzed by 2-dimensional electrophoresis and identified several proteins, including L-plastin, as highly expressed. We examined L-plastin and tissue factor (TF) expression by immunohistochemical and immunofluorescence analyses. To examine the role of L-plastin in eosinophils, we knocked down L-plastin expression in Eol-1 cells by using siRNA transfection.Results: L-plastin protein levels in nasal polyp tissue were increased in patients with NERD relative to those in patients with aspirin tolerant CRSwNP. Immunofluorescence analysis revealed that L-plastin was dominantly expressed in eosinophils and L-plastin and TF were co-expressed in eosinophils in NERD nasal polyp tissue.Knockdown of L-plastin in Eol-1 cells disrupted the cell surface distribution of TF by stimulation with granulocyte macrophage colony-stimulating factor. Conclusion:Increased expression of L-plastin by eosinophils may contribute to abnormal fibrin deposition through TF translocation to the eosinophil cell surface in NERD nasal polyp tissue, which in turn may contribute to the pathogenesis of NERD.Abbreviations: 2D-DIGE, 2-dimensional fluorescence-based difference gel electrophoresis; CRSwNP, chronic rhinosinusitis with nasal polyp

show abstract

Tissue Factor and Tissue Factor Pathway Inhibitor in Nasal Mucosa and Nasal Secretions of Chronic Rhinosinusitis with Nasal Polyp

Abstract: By upregulating the coagulation system, TF and TFPI play an important role in the pathogenesis of CRSwNP.

Cited by 37 publications

References 32 publications

Highly multiplexed proteomic analysis reveals significant tissue and exosomal coagulation pathway derangement in chronic rhinosinusitis with nasal polyps

Highly multiplexed proteomic analysis reveals significant tissue and exosomal coagulation pathway derangement in chronic rhinosinusitis with nasal polyps

Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer

Increased expression of L‐plastin in nasal polyp of patients with nonsteroidal anti‐inflammatory drug‐exacerbated respiratory disease

Contact Info

Product

Resources

About