New therapeutic targets for oral squamous cell carcinoma (OSCC) are urgently needed. We conducted genome-wide CRISPR-Cas9 screens in 21 OSCC cell lines, primarily derived from Asians, to identify genetic vulnerabilities that can be explored as therapeutic targets. We identify known and novel fitness genes and demonstrate that many previously identified OSCC-related cancer genes are non-essential and could have limited therapeutic value, while other fitness genes warrant further investigation for their potential as therapeutic targets. We validate a distinctive dependency on YAP1 and WWTR1 of the Hippo pathway, where the lost-of-fitness effect of one paralog can be compensated only in a subset of lines. We also discover that OSCCs with WWTR1 dependency signature are significantly associated with biomarkers of favorable response toward immunotherapy. In summary, we have delineated the genetic vulnerabilities of OSCC, enabling the prioritization of therapeutic targets for further exploration, including the targeting of YAP1 and WWTR1.
Matrix metalloproteinase 13 (MMP13) plays a central role in the MMP activation cascade that enables degradation of the extracellular matrix and basement membranes, and it is identified as a potential driver in oral carcinogenesis. Therefore, this study aims to determine the copy number, mRNA, and protein expression of MMP13 in oral squamous cell carcinoma (OSCC) and to associate these expressions with clinicopathological parameters. Copy number, mRNA, and protein expression analysis of MMP13 were determined using real-time quantitative PCR and immunohistochemistry methods in OSCC samples. The correlations between MMP13 expressions and clinicopathological parameters were evaluated, and the significance of MMP13 as a prognostic factor was determined. Despite discrepancies between gene amplification and mRNA and protein overexpression rates, OSCC cases showed high amplification of MMP13 and overexpression of MMP13 at both mRNA and protein levels. High level of MMP13 protein expression showed a significant correlation with lymph node metastasis (P = 0.011) and tumor staging (P = 0.002). Multivariate Cox regression model analysis revealed that high level of mRNA and protein expression of MMP13 were significantly associated with poor prognosis (P < 0.050). Taken together, these observations indicate that the MMP13 protein overexpression could be considered as a prognostic marker of OSCC.
Brucea javanica, Azadirachta indica, and Typhonium flagelliforme are medicinal plants commonly used to treat conditions associated with tumour formation. This study aimed to determine the antiproliferative activity of these plants extracts on KB and ORL-48 oral cancer cell lines and to suggest their mode of cell death. The concentration producing 50% cell inhibition (IC50) was determined and the activity was examined under an inverted microscope. Immunohistochemistry fluorescent staining method (TUNEL) was performed to indicate the mechanism of cell death and the fragmented DNA band pattern produced was obtained for verification. Compared to Azadirachta sp. and Typhonium sp., the antiproliferative activity of Brucea sp. extract was the most potent on both KB and ORL-48 cells with IC50 of 24.37 ± 1.75 and 6.67 ± 1.15 µg/mL, respectively. Signs of cell attrition were observed 24 hr after treatment. Green fluorescent spots indicating cell death by apoptosis were observed in images of both cells following treatment with all the three extracts. DNA fragments harvested from Brucea-treated cells produced bands in a ladder pattern suggesting the apoptotic effect of the extract. It is thus concluded that Brucea sp. extract exhibited cytotoxic activity on ORL-48 cells and their action mechanism is via apoptosis.
The prevalence rate of 749 cases of oral squamous cell carcinomas (SCC) recorded between 1978-1984 was studied. Results showed that the Indians formed the dominant group (63.8%) followed by the Malays (19.6%) and Chinese (16.6%). The peak incidences were generally located between the sixth and eighth decades. Only in the Chinese group a male preponderance was noted. In the Indians, the buccal mucosa was the most prevalent site; in the Malays and Chinese males, the gingiva and alveolus; and the Chinese female, the tongue. In all three groups, the well-differentiated SCC was the commonest type and the poorly differentiated least common.
The presence of cutaneous metastases in squamous cell carcinomas of the head and neck (SCCHN) is rare and associated with a dismal prognosis. It is vital to distinguish these lesions from direct invasion of the skin by SCCHN or primary cutaneous malignancies as the prognosis is vastly different and so is the management. In this case report, we present four cases of cutaneous metastases and also briefly review the literature pertaining to this phenomenon.
Pectoralis major myocutaneous flap reconstruction of the defect following surgery for oral cancer in fourteen patients is described. The problems and complications encountered have been found to be minimal. Functional and cosmetic results were acceptable.
Carcinoma of the buccal mucosa is the commonest intra-oral malignancy seen in Malaysia. The purpose of this paper is to present 12 patients with carcinoma of the buccal mucosa who were seen by the authors between January 1981 to September 1981. The principal problems are those of late presentation and treatment, these aspects are illustrated, with a view of early return to normal life.
Squamous cell carcinoma is the commonest malignant tumour of the mouth (91 percent) in people living in Peninsular Malaysia. Since the histological grading of oral carcinoma ·is one of the several important factors to be considered in the long term survival of patients a more detailed study of anaplastic carcinoma of the mouth in 100 patients is made in this study. As reported in an earlier study the Chinese seem to be more prone to develop anaplastic carcinoma of the mouth. In contrast although oral carcinoma occurs most commonly in the Indians, the development of anaplastic carcinoma seems to be the least in them. The Indians seem to have a better host immune response to oral carcinoma than the Chinese and the Malays occupy an intermediary position. The peak age incidence was between 51-70 years (50 percent). In descending order of frequency anaplastic carcinoma involved the gingiva (29 percent), buccal mucosa (22 percent), palate (20 percent), and tongue (16 percent). Further studies may help to formulate a more effective tailor-made regime of treatment for each individual oral carcinoma patient.