MyMedR

The opposing roles of NOTCH signalling in head and neck cancer: a mini review

Yap LF, Lee D, Khairuddin A, Pairan MF, Puspita B, Siar CH, et al.

Oral Dis, 2015 Oct;21(7):850-7.

NOTCH signalling can exert oncogenic or tumour suppressive effects in both solid and haematological malignancies. Similar to T-cell acute lymphoblastic leukaemia (T-ALL), early studies suggested a pro-tumorigenic role of NOTCH in head and neck squamous cell carcinoma (HNSCC), mainly based on the increased expression levels of the genes within the pathway. Recently, data from exome sequencing analyses unexpectedly pointed to a tumour suppressor role for NOTCH in HNSCC by identifying loss-of-function mutations in the NOTCH1 gene in a significant proportion of patients. These data have questioned the accepted role of NOTCH in HNSCC and the possible rationale of targeting NOTCH in this disease. This review summarises the current information on NOTCH signalling in HNSCC and discusses how this pathway can apparently exert opposing effects within the same disease.

Periodontal response to two intracanal medicaments in replanted monkey incisors

Thong YL, Messer HH, Siar CH, Saw LH

Dent Traumatol, 2001 Dec;17(6):254-9.

PMID: 11766092

Intracanal medicaments are recommended for use in replanted teeth to inhibit inflammatory root resorption. This study compared the effect of calcium hydroxide (Pulpdent) and a corticosteroid-antibiotic paste (Ledermix) on periodontal healing and root resorption following replantation. Incisors of eight Macaca fascicularis monkeys were extracted, stored dry for 15 min and replanted. After 11 days, root canals in two adjacent maxillary incisors were treated with one medicament and contralateral incisors with the other medicament, or left as untreated controls. Animals were sacrificed 8 weeks later and the teeth prepared for histomorphometric evaluation of periodontal ligament inflammation and root resorption. Periodontal ligament inflammation and inflammatory root resorption were markedly inhibited by both calcium hydroxide and corticosteroid-antibiotic relative to untreated controls. Replacement resorption was lowest in the corticosteroid-antibiotic group, and significantly (P<0.05) more normal periodontal ligament was present in this group (79.6%) than in calcium hydroxide and control groups (64.6% and 62.7%, respectively). Treatment with the corticosteroid-antibiotic inhibited inflammatory resorption and was slightly more effective than calcium hydroxide in producing a periodontal healing response.

Parenchyma-stromal interactions induce fibrosis by secreting CCN2 and promote osteoclastogenesis by stimulating RANKL and CD68 through activated TGF-β/BMP4 in ameloblastoma

Takebe Y, Tsujigiwa H, Katase N, Siar CH, Takabatake K, Fujii M, et al.

J Oral Pathol Med, 2017 Jan;46(1):67-75.

PMID: 27327904 DOI: 10.1111/jop.12467

BACKGROUND: Tumor parenchyma-stromal interactions affect the properties of tumors and their dynamics. Our group previously showed that secreted frizzled related protein (sFRP)-2 impairs bone formation and promotes bone invasion in ameloblastoma. However, the effects of the secreted growth factors CCN2, TGF-β, and BMP4 on stromal tissues in ameloblastoma remain unclear.

MATERIALS AND RESULTS: Thirty-five paraffin-embedded ameloblastoma cases, ameloblastoma-derived cell lines (AM-1), and primary cultures of ameloblastoma stromal fibroblasts (ASF) were used. Immunohistochemistry, MTT assay, Western blotting, and RT-PCR were performed on these samples. Parenchyma-stromal CCN2 overexpression correlated significantly with fibrous-type stroma, but not with myxoid-type stroma, suggesting a role of CCN2 in fibrosis (P < 0.05). Recombinant CCN2 induction of enhanced ASF proliferation in AM-1 medium supports this view. Conversely, BMP4 and TGF-β were expressed in myxoid-type fibroblasts, but little expression was found in parenchyma. RANKL-positive and CD68-positive stromal cell populations were significantly greater in myxoid-type tumor areas than in fibrous-type tumor areas, while a higher Ki-67 labeling index was recorded in ameloblastoma with fibrous-type stroma. These data suggest that stromal properties influence bone resorption-related activities and growth rates, respectively.

CONCLUSIONS: These results suggest that the effects of secreted growth factors are governed by ameloblastoma parenchyma-stromal interactions. CCN2 promotes fibrogenesis independent of TGF-β signaling. Absence of CCN2 expression is associated with a phenotypic switch to a myxoid-type microenvironment that is conducive for TGF-β/BMP4 signaling to promote osteoclastogenesis.

Influence of abutment design on clinical status of peri-implant tissues

Taiyeb-Ali TB, Toh CG, Siar CH, Seiz D, Ong ST

Implant Dent, 2009 Oct;18(5):438-46.

PMID: 22129962 DOI: 10.1097/ID.0b013e3181ad8e7a

To compare the clinical soft tissue responses around implant tooth-supported 3-unit bridges using tapered abutments with those using butt-joint abutments.

Calcifying fibroblastic granuloma. A case report

Taiyeb Ali TB, Siar CH

J N Z Soc Periodontol, 1997.

PMID: 9522721

Comparative assessment of the interfacial soft and hard tissues investing implants and natural teeth in the macaque mandible

Siar CH, Toh CG, Romanos GE, Ng KH

Clin Oral Investig, 2015 Jul;19(6):1353-62.

PMID: 25411082 DOI: 10.1007/s00784-014-1362-7

The aim of this study was to conduct a comparative qualitative and quantitative assessment of the interfacial soft and hard tissues investing implants and natural teeth.

RANK, RANKL, and OPG in recurrent solid/multicystic ameloblastoma: their distribution patterns and biologic significance

Siar CH, Tsujigiwa H, Ishak I, Hussin NM, Nagatsuka H, Ng KH

Oral Surg Oral Med Oral Pathol Oral Radiol, 2015 Jan;119(1):83-91.

PMID: 25446507 DOI: 10.1016/j.oooo.2014.09.017

To determine the distribution patterns of bone resorption regulators, receptor activator of nuclear factor κ-B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in recurrent ameloblastoma (RAs) and to clarify their impact on the biologic behavior of these neoplasms.

Intra-epithelially entrapped blood vessels in ameloblastoma

Siar CH, Ishak I, Ng KH

J Oral Pathol Med, 2015 May;44(5):378-85.

PMID: 25155411 DOI: 10.1111/jop.12247

The ameloblastoma is a benign but locally aggressive odontogenic neoplasm with a high recurrence rate. While significant progress has been made in our understanding regarding the role of tumoral vasculature relative to the diverse behavioral characteristics of this tumor, no attention has been paid to a distinct subset of blood vessels entrapped within its epithelial compartment. As vascular niches are known to influence tumoral growth, clarification of these vessels is important. The objectives of this study were to investigate the morphologic characteristics of intra-epithelially entrapped blood vessels (IEBVs) in ameloblastoma and to speculate on their relevance.

Podoplanin, E-cadherin, β-catenin, and CD44v6 in recurrent ameloblastoma: their distribution patterns and relevance

Siar CH, Ishak I, Ng KH

J Oral Pathol Med, 2015 Jan;44(1):51-8.

PMID: 25059841 DOI: 10.1111/jop.12203

Ameloblastoma is a benign but locally infiltrative odontogenic epithelial neoplasm with a high risk for recurrence. Podoplanin, a lymphatic endothelium marker, putatively promotes collective cell migration and invasiveness in this neoplasm. However, its role in the recurrent ameloblastoma (RA) remains unclear. As morphological, signaling, and genetic differences may exist between primary and recurrent tumors, clarification of their distribution patterns is of relevance.

Identifying factors associated with diagnostic concordance/discordance in oral lichen planus

Siar CH, Lim JS, Tang SP, Chia HS, Loh YM, Ng KH

J Oral Maxillofac Surg, 2013 Oct;71(10):1688-93.

PMID: 23773425 DOI: 10.1016/j.joms.2013.04.026

To identify factors associated with concordance and discordance between clinical and histopathologic diagnoses of oral lichen planus lesions.

Differential expression of transcription factors Snail, Slug, SIP1, and Twist in ameloblastoma

Siar CH, Ng KH

J Oral Pathol Med, 2014 Jan;43(1):45-52.

PMID: 23560539 DOI: 10.1111/jop.12065

Epithelial-to-mesenchymal transition (EMT) via the mechanism of transcription repression is a crucial process for the induction of invasiveness in many human tumors. Ameloblastoma is a benign odontogenic epithelial neoplasm with a locally infiltrative behavior. Twist, an EMT promoter, has been implicated in its invasiveness. The roles of the other transcription factors remain unclarified.

Claudin expression and tight junction protein localization in the lining epithelium of the keratocystic odontogenic tumors, dentigerous cysts, and radicular cysts

Siar CH, Abbas SA

Oral Surg Oral Med Oral Pathol Oral Radiol, 2013 May;115(5):652-9.

PMID: 23601220 DOI: 10.1016/j.oooo.2013.02.013

The aim of this study was to evaluate the expression and localization of tight junction proteins (TJPs) or claudins in the keratocystic odontogenic tumor (KCOT) and to correlate with its biological behavior.

Cementum status in natural teeth opposing implant-borne bridgework in Macaca fascicularis

Siar CH, Pua CK, Toh CG, Romanos G, Ng KH

Oral Surg Oral Med Oral Pathol Oral Radiol, 2012 Nov;114(5 Suppl):S46-53.

PMID: 23083955 DOI: 10.1016/j.tripleo.2011.07.049

The objective of this study was to investigate the cementum status in natural teeth opposing implant-supported bridgework.

Differential expression of canonical and non-canonical Wnt ligands in ameloblastoma

Siar CH, Nagatsuka H, Han PP, Buery RR, Tsujigiwa H, Nakano K, et al.

J Oral Pathol Med, 2012 Apr;41(4):332-9.

PMID: 22077561 DOI: 10.1111/j.1600-0714.2011.01104.x

Canonical and non-canonical Wnt signaling pathways modulate diverse cellular processes during embryogenesis and post-natally. Their deregulations have been implicated in cancer development and progression. Wnt signaling is essential for odontogenesis. The ameloblastoma is an odontogenic epithelial neoplasm of enamel organ origin. Altered expressions of Wnts-1, -2, -5a, and -10a are detected in this tumor. The activity of other Wnt members remains unclarified.

Prevalence of bilateral 'mirror-image' lesions in patients with oral potentially malignant epithelial lesions

Siar CH, Mah MC, Gill PP

Eur Arch Otorhinolaryngol, 2012 Mar;269(3):999-1004.

PMID: 21789676 DOI: 10.1007/s00405-011-1712-x

Early detection of oral potentially malignant epithelial lesions (PMELs) is aimed at improving survival rates as carcinogenesis is a multistep process and prevention is possible if these lesions are detected at an early and reversible stage of the disease. A prospective clinical study aimed at determining the prevalence of bilateral 'mirror-image' oral PMELs was carried out. Sample consisted of 32 (53.3%) Indians, 23 (38.3%) Chinese, 4 (6.7%) Malays and one (1.7%) Nepalese. All had histopathological confirmation of their primary existing PMEL as inclusion criteria. A total of 70 primary lesions were detected. The most common PMEL found was oral lichen planus. Of these, 28 (46.7%) patients exhibited bilateral 'mirror-image' lesions (n = 42) either synchronously (n = 32/42) or metachronously (n = 10/42). The remaining 32 (53.3%) patients had normal-looking contralateral mucosa. Present findings suggest that patients presenting with oral PMELs are at greater risk of developing a second lesion, most probably in the contralateral 'mirror-image' site.

Dimensional profile of oral mucosa around combined tooth-implant-supported bridgework in macaque mandible

Siar CH, Toh CG, Ali TB, Seiz D, Ong ST

Clin Oral Implants Res, 2012 Apr;23(4):438-46.

PMID: 21435011 DOI: 10.1111/j.1600-0501.2010.02145.x

A stable oral mucosa is crucial for long-term survival and biofunctionality of implants. Most of this evidence is derived from clinical and animal studies based solely on implant-supported prosthesis. Much less is known about the dimensions and relationships of this soft tissue complex investing tooth-implant-supported bridgework (TISB). The aim here was to obtain experimental evidence on the dimensional characteristics of oral mucosa around TISB with two different abutment designs.

Risk of the contralateral mucosa in patients with oral potentially malignant disorders

Siar CH, Mah MC, Gill PP

Asian Pac J Cancer Prev, 2011;12(3):631-5.

PMID: 21627356

BACKGROUND: It is known that abnormal changes may occur in any part of the oral mucous membrane exposed to a carcinogen. Therefore patients with oral potentially malignant disorders (PMDs) are at risk of developing similar lesions at multiple sites.

OBJECTIVES: To determine the risk of the contralateral mucosa in patients presenting with oral PMDs.

MATERIALS AND METHODS: Sixty individuals with PMDs were selected for this study. These comprised 32 (53.3%) Indians, 23 (38.3%) Chinese, four (6.7%) Malays and one (1.7%) Nepalese. All selected cases had histopathological confirmation of their primary existing lesion as inclusion criteria. Cases that subsequently presented with a lesion in the corresponding anatomical site also underwent scalpel incisional biopsy on this second lesion to verify its diagnosis. The remaining cases that presented with unilateral PMDs at the time of study were subjected to a cytobrush biopsy on the normal looking contralateral mucosa.

RESULTS: A total of 70 primary PMDs were detected in 60 patients. The most common PMD found was oral lichen planus (n=40, 57.1%). Of the 60 patients studied, 28 (46.6%) exhibited bilateral lesions either synchronously (n=21, 35.0%) or metachronously (n=7, 11.6%). The remaining cases that had undergone cytobrush biopsy on the corresponding anatomical site yielded normal cytological results.

CONCLUSIONS: Present findings demonstrated that patients presenting with PMDs in the upper aerodigestive tract are at a greater risk of developing a second lesion most probably in the contralateral anatomical site.

Ameloblastoma of the jaws: a retrospective analysis of 340 cases in a Malaysian population

Siar CH, Lau SH, Ng KH

J Oral Maxillofac Surg, 2012 Mar;70(3):608-15.

PMID: 21723654 DOI: 10.1016/j.joms.2011.02.039

Ameloblastoma of the human jaw is an uncommon but clinically significant odontogenic epithelial neoplasm. The aim was to analyze the clinicopathologic characteristics of ameloblastoma in a Malaysian population.

Subcutaneous reactions and degradation characteristics of collagenous and noncollagenous membranes in a macaque model

Siar CH, Toh CG, Romanos G, Ng KH

Clin Oral Implants Res, 2011 Jan;22(1):113-20.

PMID: 20678135 DOI: 10.1111/j.1600-0501.2010.01970.x

collagenous and noncollagenous membranes have been investigated in many animal systems but their effects in the macaque model are unknown.

Notch4 overexpression in ameloblastoma correlates with the solid/multicystic phenotype

Siar CH, Nagatsuka H, Chuah KS, Rivera RS, Nakano K, Ng KH, et al.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2010 Aug;110(2):224-33.

PMID: 20659700 DOI: 10.1016/j.tripleo.2010.03.009

Notch signaling has been implicated in cell fate decisions during odontogenesis and tumorigenesis of some odontogenic neoplasms; however, its role in solid/multicystic (SA), unicystic (UA), and recurrent (RA) ameloblastoma remains unclear. The aim of this study was to determine Notch receptor and ligand expressions in these subtypes and to speculate on their significance.

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