The Role of Fibroblast Activation in Uterine Fibroid

NCT03444987 | Completed

• 1 other identifier: UF
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Uterine fibroids (UFs), also called uterine leiomyomas or myomas, are steroid hormone-responsive, benign tumors of the smooth muscle compartment (myometrium) of the uterus. They are the most common neoplasm affecting women in their reproductive age. It is estimated that up to 77% of women develop UF in their life. UFs are one of the leading causes of hospitalisations for gynaecological disorders and are the most frequent reason for hysterectomy. According to relevant literature, 40%-60% of all the hysterectomies performed are due to the presence of UFs.

Conditions

Uterine Fibroid

Keywords

Uterine fibroid; FAP; Autophagy

Outcome Measures

Primary Outcomes (1)

• Comparing FAP and autophagy markers in patient and control groups.

  Explore difference in level of fibroblast activation marker (FAP) and autophagy markers (LC3 and P62) in UF tissue samples compared to normal myometrial samples (1 cm from the UF lesion).

  1 year

Secondary Outcomes (1)

• Study signaling pathway linking FAP and autophagy which ma considered as a therapeutic target

  1 year

Study Arms (2)

patients group

include 35 pre-menopausal women (age ˂ 50 years) enrolled to undergo hysterectomy for symptomatic UF at the women health hospitals, Assiut University. * The protein expression of the followings markers will be estimated in tumor tissue samples: 1. Fibroblast activation protein (FAP) will be measured by quantitative real time polymerase chain reaction qRTPCR (mRNA level) and ELISA (protein level). 2. Autophagy markers level (LC3 and p62) will be measured by qRTPCR (mRNA level) and by immunohistochemical analysis. 3. Phosphorylated protein kinase B (pAKT ) by ELISA (protein level). analysis. 4. Markers of oxidative stress (Malondialdehyde as lipid peroxide) by a colorimetric method. 5. Reduced glutathione, an antioxidant marker by a colorimetric method .

Genetic: Measurement of protein expression in tissues.

Control group

include 35 normal myometrial tissue samples obtained 1 cm away from the fibroid capsule from the same patients. * The protein expression followings markers will be estimated in normal myometrial tissue samples 1. Fibroblast activation protein (FAP) will be measured by quantitative real time polymerase chain reaction qRTPCR (mRNA level) and ELISA (protein level). 2. Autophagy markers level (LC3 and p62) will be measured by qRTPCR (mRNA level) and by immunohistochemical analysis. 3. Phosphorylated protein kinase B (pAKT) by ELISA (protein level). 4. Markers of oxidative stress (Malondialdehyde as lipid peroxide) by a colorimetric method. 5. Reduced glutathione, an antioxidant marker by a colorimetric method .

Genetic: Measurement of protein expression in tissues.

Interventions

Measurement of protein expression in tissues. GENETIC

The followings markers will be estimated in tissue 1. FAP, a marker of fibroblast activation, using quantitative real time polymerase chain reaction qRTPCR (mRNA level) and ELISA (protein level). 2. Markers of autophagy including LC3 and p62 using qRTPCR (mRNA level) and by immunohistochemical analysis. 3. Phosphorylated protein kinase B (pAKT) level by ELISA (protein level). 4. Markers of oxidative stress (Malondialdehyde as lipid peroxide) by a colorimetric method. 5. Reduced glutathione, an antioxidant marker by a colorimetric method

Control group; patients group

Eligibility Criteria

• Age: Up to 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

This study will include 35 premenopausal women (age ˂ 50 year) with uterine fibroids who are diagnosed through clinical gynecological, ultrasound and other auxiliary examinations. All selected patients will exhibit a normal coagulation function.

You may qualify if:

• i. Premenopausal women (age ˂ 50) with uterine fibroids who are diagnosed through clinical gynecological, ultrasound and other auxiliary examinations.
• ii. Patients who exhibit a normal coagulation function.

You may not qualify if:

• i. Patients who have a previous history of myomectomy or with ovarian malignancy and borderline tumors ii. Patients who are subsequently diagnosed with uterine adenomyosis. iii. Pregnant women. iv. Patients who receive hormonal treatment within three months before surgery. v. Patients with history of coronary artery disease, hypertension, liver cirrhosis or hematologic disorders.

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assiut university -Faculty of medicine- Departement of Biochemistry

Asyut, 71111, Egypt

Location

Related Publications (8)

• McWilliams MM, Chennathukuzhi VM. Recent Advances in Uterine Fibroid Etiology. Semin Reprod Med. 2017 Mar;35(2):181-189. doi: 10.1055/s-0037-1599090. Epub 2017 Mar 9.

  PMID: 28278535 BACKGROUND

• Moore AB, Yu L, Swartz CD, Zheng X, Wang L, Castro L, Kissling GE, Walmer DK, Robboy SJ, Dixon D. Human uterine leiomyoma-derived fibroblasts stimulate uterine leiomyoma cell proliferation and collagen type I production, and activate RTKs and TGF beta receptor signaling in coculture. Cell Commun Signal. 2010 Jun 10;8:10. doi: 10.1186/1478-811X-8-10.

  PMID: 20537183 BACKGROUND

• Rasanen K, Vaheri A. Activation of fibroblasts in cancer stroma. Exp Cell Res. 2010 Oct 15;316(17):2713-22. doi: 10.1016/j.yexcr.2010.04.032. Epub 2010 May 6.

  PMID: 20451516 BACKGROUND

• Wang H, Wu Q, Liu Z, Luo X, Fan Y, Liu Y, Zhang Y, Hua S, Fu Q, Zhao M, Chen Y, Fang W, Lv X. Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma. Cell Death Dis. 2014 Apr 10;5(4):e1155. doi: 10.1038/cddis.2014.122.

  PMID: 24722280 BACKGROUND

• Islam MS, Ciavattini A, Petraglia F, Castellucci M, Ciarmela P. Extracellular matrix in uterine leiomyoma pathogenesis: a potential target for future therapeutics. Hum Reprod Update. 2018 Jan 1;24(1):59-85. doi: 10.1093/humupd/dmx032.

  PMID: 29186429 BACKGROUND

• Luo N, Guan Q, Zheng L, Qu X, Dai H, Cheng Z. Estrogen-mediated activation of fibroblasts and its effects on the fibroid cell proliferation. Transl Res. 2014 Mar;163(3):232-41. doi: 10.1016/j.trsl.2013.11.008. Epub 2013 Nov 20.

  PMID: 24316382 BACKGROUND

• Bainbridge TW, Dunshee DR, Kljavin NM, Skelton NJ, Sonoda J, Ernst JA. Selective Homogeneous Assay for Circulating Endopeptidase Fibroblast Activation Protein (FAP). Sci Rep. 2017 Oct 2;7(1):12524. doi: 10.1038/s41598-017-12900-8.

  PMID: 28970566 BACKGROUND

• Hamson EJ, Keane FM, Tholen S, Schilling O, Gorrell MD. Understanding fibroblast activation protein (FAP): substrates, activities, expression and targeting for cancer therapy. Proteomics Clin Appl. 2014 Jun;8(5-6):454-63. doi: 10.1002/prca.201300095. Epub 2014 Mar 24.

  PMID: 24470260 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Tissue samples included * 35 UF samples (myoma) collected from the patients who had hysterectomy for symptomatic UFs following confirmation of diagnosis clinically and by ultrasound. UF samples were collected from fibroids 4-6 cm in size. * 35 normal myometrial tissue samples obtained 1 cm away from the fibroid capsule from the same patients

MeSH Terms

Conditions

Leiomyoma

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Nashwa AbdelGhfar El Maghraby, MD student)

  Assiut University

  PRINCIPAL INVESTIGATOR

• Eman Magdy Mohamed, Lecturer

  Assiut University

  STUDY DIRECTOR

• Ahmed Mohamed Abass, Lecturer

  Assiut University

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Study Record Dates

• First Submitted: February 20, 2018
• First Posted: February 26, 2018
• Study Start: March 1, 2018
• Primary Completion: November 1, 2019
• Study Completion: March 1, 2020
• Last Updated: February 9, 2021

Record last verified: 2021-02

Locations

EG (1)