Oral Submucous Fibrosis Clinical Trial
Official title:
Risk Assessment of Malignant Transformation in Oral Submucous Fibrosis Using Epithelial Mesenchymal Transition (EMT) Signatures in Tissue Samples and Saliva
Oral Sub mucous Fibrosis (OSMF) is essentially an imbalance between collagen metabolism and
wound healing mechanism induced by arecanut chewing habit. Clinically the disease progresses
in stages with patients presenting with burning sensation, intolerance to spicy food,
vesicles particularly on the palate, ulceration and dryness of the mouth , fibrosis of the
oral mucosa, leading to lips, tongue, and palate rigidity and finally trismus. As the disease
is progressively debilitating and has potential to turn in to malignant cancer a study was
designed to assess if there any tissue or saliva markers that can be assessed for early
diagnosis and indicate malignant transformation if any.
Participants who had OSMF and habit history, patients without OSMF but habit history formed
the case group where as normal patients without OSMF and no habit history were in control
group. Eligible candidates who consented to participate in study were subjected to biopsy
procedure and also their saliva samples were collected. Biopsy samples were subjected to
immunohistochemistry (IHC) and polymerase chain reaction (PCR) to assess the EMT markers like
vimentin, e-cadherin and collagen IV. miRNA copies were extracted from saliva and were
subjected RT-PCR.
Research question was:
1. Is EMT a positive signature in OSMF.
2. Does histopathological grading and dysplasia in OSMF have any correlation with EMT.
3. Can aberrant EMT markers be a reliable indicator for risk assessment of early malignant
transformation.
4. Can expression of mi RNA 21 in saliva predict the disease severity and more importantly
assess risk of early malignant transformation in OSMF.
Epithelial-mesenchymal transition (EMT) describes the process whereby cells shed their
epithelial properties and adopt a more mesenchymal and invasive phenotype. A continuous
molecular cross talk between epithelial and mesenchymal cells is required during embryonic
development (epithelial mesenchymal transition) and probably plays an important role in
pathologic process like wound healing and tumour progression. The development of carcinomas
is due to the genetic changes within the target epithelium. As there is conversion of normal
epithelium to potentially malignant and to squamous cell carcinoma, the stroma also changes
from normal to activated or tumor associated called as the stromal reaction. 10 EMT can
generate mesenchymal cells that express α-smooth muscle actin (αSMA), as seen in
myofibroblasts. It is, however, unclear whether functional myofibroblasts seen in fibrosis or
cancer derived from epithelial or endothelial cells
Hence EMT markers in OSMF were assessed in this study. the following markers chosen as:
1. miRNA-21 regulates cell proliferation, apoptosis and the epithelial to mesenchymal
transition during neoplastic progression and is up regulated in a variety of cancers.An
increased expression of miRNA-21 is seen in myofibroblasts.12 Since we know the role of
myofibroblasts in OSMF, salivary expression of mi RNA- 21 was included as marker.
2. Type IV collagen has the unique feature of self-associating through intramolecular
covalent bonds, providing barrier and mechanical strength properties to basement
membranes.The increased collagen deposition in OSMF involves numerous fibroblasts that
are converted to myofibroblasts found in histologic sections of tissue specimens. an
altered micro environment or stroma such as persistent myofibroblasts has been shown to
result in tumorigenesis and tumor progression
3. Cadherins are a class of type-1 trans-membrane proteins known for its calcium-dependent
cell-cell adhesion property. E-cadherins are members of this protein family found in
epithelial cells which serve important roles in cell adhesion by ensuring that cells
within tissues are bound together. The loss of E-cadherin function or expression has
been implicated in cancer progression and metastasis.E-cadherin expression in the head
and neck epithelium is essential for the morphogenesis and homeostasis of epithelial
tissues. The cadherin-mediated cell-cell contacts are required for the
anchorage-dependent growth of epithelial cells.
Hence lower expression of E- cadherin is a sign of loss of epithelial integrity
4. The intermediate filament protein vimentin is involved in the regulation of cell
behavior, morphology, and mechanical properties. Vimentin is a EMT marker expressed in
connective tissue. Expression of vimentin in epithelium is a positive signature of EMT,
and its evaluation in OSMF can unveil the importance of EMT signature in oral fibrosis.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04153266 -
Oral Epithelial Dysplasia Informational Needs Questionnaire
|
||
Not yet recruiting |
NCT06332612 -
Metformin Repurposing in Oral Submucous Fibrosis: Unveiling In Vitro Signaling Pathways, Progressing to Clinical Trial
|
Phase 1/Phase 2 | |
Completed |
NCT02711046 -
Use of Single Staged Nasolabial Flap in Oral Submucous Fibrosis
|
N/A | |
Completed |
NCT03011086 -
Evaluation of Auto Antibodies in Oral Sub Mucous Fibrosis
|
N/A | |
Recruiting |
NCT03511261 -
Efficacy of Curcumin in Oral Submucous Fibrosis
|
Phase 2 | |
Completed |
NCT04476420 -
Comparative Effect of Nigella Sativa and Conventional Management for OSMF
|
Phase 3 | |
Active, not recruiting |
NCT02645656 -
Topical Application of Curcumin Orabase in Oral Submucous Fibrosis (OSMF)
|
Phase 2 | |
Not yet recruiting |
NCT04487938 -
Oral Cancer Screening and Education in Hong Kong
|