Differential Regulation of Innate Lymphoid Cells in Human and Murine Oral Squamous Cell Carcinoma.

Oral squamous cell carcinomas (OSCC) remain a major healthcare burden in Asian countries. In Pakistan alone, it is the most common cancer in males and second only to breast cancer in females. Alarmingly, treatment options for OSCC remain limited. With this context, investigations made to explore the inflammatory milieu of OSCC become highly relevant, with the hope of practicing immunotherapeutic approaches to address this highly prevalent tumor. We investigated the newly identified innate lymphoid cells (ILCs) and associated cytokines in well-defined human oral squamous cell carcinoma (OSCC) as well as in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced murine model of OSCC using flow cytometry and quantitative real-time polymerase chain reaction (qPCR). We further went on to explore molecular circuitry involved in OSCC by developing a murine model of OSCC and using an α-Thy1 antibody to inhibit ILCs. Amongst the ILCs that we found in human OSCC, ILC3 (23%) was the most abundant, followed by ILC2 (17%) and ILC1 (1%). Mice were divided into four groups: DMBA (n = 33), DMBA+antibody (Ab) (n = 30), acetone (n = 5), and control (n = 5). In murine OSCC tissues, ILC1 and ILC3 were down-infiltrated, while ILC2 remained unchanged compared to controls. Interestingly, compared to the controls (DMBA group), mice treated with the α-Thy1 antibody showed fewer numbers of large tumors, and a larger percentage of these mice were tumor-free at this study's end point. We present novel data on the differential expansion/downsizing of ILCs in OSCC, which provides a pivotal basis to dive deeper into molecular circuitry and the OSCC tumor niche to devise novel diagnostic, therapeutic, and prognostic strategies to prevent/treat oral cancers.

Quantitative Analyses of Skin Cancer Research in Pakistan.

In order to investigate the current status of skin cancer research output in Pakistan, International (PubMed) and national (PakMediNet) scientific databases were searched using variety of keywords to retrieve relevant publications. A strict inclusion criterion was applied to select skin cancer publications for final analyses. Data were recorded by two authors and consistent data were entered into SPSS and Microsoft Excel and analyzed for annual growth rate and frequencies. Of 116 articles that were finally included in the study, 74 were original articles, 24 were case-reports, 10 were review articles, three were editorials, two were research communications and one each of case-series, correspondence and response to letter to the editor. The first article on skin cancer from Pakistan was published in 1976 whereas the last article included in our study was published in December 2018. Excluding Karachi, most of the cities have no contribution in the field of skin cancer. Since 1976 to date, the average number of publications per year has been low, with only 2.7 publications per year. Skin cancer research is alarmingly scarce in Pakistan. This calls for immediate attention by all concerned to contribute and devise appropriate measures towards skin cancer research in Pakistan.

Correlation of ABH blood group antigens secretion with Helicobacter pylori infection in Pakistani patients.

OBJECTIVES: A and B blood group antigens are fucosylated carbohydrate present on human erythrocytes and body secretions. Their presence in body secretions depends on the expression of a dominant allele of secretor gene FUT2 and is correlated with susceptibility to various infectious and non-infectious diseases. We investigated the correlation of blood group and ABH antigen secretion with Helicobacter pylori infection and gastroduodenal symptoms and analysed the distribution of babA gene among ABH secretors and non-secretors. METHODS: Two hundred and ninety patients who underwent gastroduodenal endoscopy during 2011 to 2012 participated. Gastric biopsy, saliva and blood samples were obtained from every patient. Gastric biopsies were subjected to rapid urease test and PCR for the detection of H. pylori and babA gene. Blood grouping and ABH antigens secretions were determined by Lewis blood group phenotyping and haemagglutination inhibition test. RESULTS: 50.34% of patients were ABH antigen secretors and 45.51% non-secretors. Distribution analysis of blood group revealed that 40 blood group B, 67 blood group A 20 blood group O and 19 blood group AB patients secreted ABH antigens in saliva. Fifty-six blood group O, 19 blood group B, 32 blood group A and 17 blood group AB patients were non-secretors. Gastroduodenal complaints were common among non-secretors. Sixty-two percent of patients with a combination of duodenal ulcer and gastro-oesophageal reflux and 54% of patients with gastritis were non-secretors. Of 290 samples, 31.02% were positive for H. pylori. Thirty percent of these tested positive for babA gene; the majority belonged to non-secretor blood group O. CONCLUSIONS: Our results suggest that the infection of H. pylori is correlated with ABO blood groups and blood group antigens secretion in body fluids.

Comparison of light microscopy and digital microscopy for learning oral pathology practicals among second year dental students.

Background/purpose: Previous studies have shown that digital microscopy is an indispensable tool for teaching oral pathology laboratory course. Despite this, our institute relies solely on recommended/reference book images for oral pathology practicals, neglecting both light and digital microscopy methods. Gathering students' feedback on these methods is essential before considering digital microscopy as part of the oral pathology curriculum. Therefore, this study aimed to compare the usefulness of light and digital microscopy among second-year dental students. Materials and methods: The study was conducted from December 6 to December 7, 2023, in the Department of Oral Pathology, Dr. Ishrat-ul-Ibad Khan Institute of Oral Health Sciences, Dow University of Health Sciences. The study involved the selection of five cases from the oral pathology course, followed by feedback on students' diagnostic skills, learning impact and acceptance rate of light and digital microscopy using an online questionnaire. Mann-Whitney U test was used to compare students' responses and P-value < 0.05 was set as statistically significant. Results: There was a statistically significant difference in diagnostic scores between light microscopy and digital microscopy (P < 0.05). Statistically significant differences favoring digital microscopy were observed in various aspects, including interpreting variations, diagnosis, time efficiency, and image clarity. Conclusion: Although diagnostic scores were lower, digital microscopy was perceived as a useful method for enhancing diagnostic skills among dental students. Both light microscopy and digital microscopy are viable options for oral pathology practicals, however, digital microscopy was preferred by students due to its time efficiency and clear image quality.

Leadership competencies for dentists: What do undergraduate students think?

Dentists face difficult situations and challenges every day, but undergraduate dental students in Pakistan are not formally taught leadership skills or assessed for these skills. This study aims to explore the perception of undergraduate dental students on various leadership competencies. A multi-institutional cross-sectional observational study was conducted on undergraduate students in five institutions by using universal sampling technique. Students were asked to self-assess various leadership competencies for dentists based on 15 competencies using a validated questionnaire utilizing Likert scale response format. Responses to these items were presented as frequency and percentage. The overall scores were presented in mean and standard deviation and median and interquartile range. The differences in median scores of all items of the questionnaire between male and female students were determined with Mann Whitney U tests. The year-wise differences in the median of all response items of the questionnaire were determined using Kruskal Wallis H test. A total of 750 students, of which 570 (76%) were females and 180 (24%) were males, participated in the study. Most of the students (n = 708, 94.4%) did not attended any leadership course or workshop in the last five years. Majority of the students perceived that their leadership competencies were fair to excellent. Empathy was perceived as 'excellent' by the majority of the students (n = 294, 39.2%). Majority of the students (n = 319, 42.5%) perceived that their 'authenticity' skills were 'good'. Statistically significant differences were reported between male and female students in most of the leadership skills including 'compassion', 'advocacy skills', 'inquiry skills', 'empathy', 'integrity', 'ability to build trust with others', 'managing conflict', 'leading groups/teams', 'dealing with difficult personalities', and 'likelihood to exercise leadership during a crisis' (p < 0.05). There were also significant differences in the median item scores in 13 out of 15 leadership domains and the year of study (p < 0.05). The study identified the perceptions of students regarding different leadership competencies. It gives indications that which leadership competencies need to be incorporated, promoted, and enhanced in leadership curriculum to make them effective dental practitioners and leaders in future. Incorporating these targeted leadership courses into the curriculum can provide participants with the opportunity to refine their existing leadership strengths and develop a well-rounded set of competencies essential for making a significant contribution in their chosen fields.

Comparison of virtual clinical scenario and role play in learning oral pathology among dental students.

In oral pathology, virtual clinical scenario illustrating dentist-patient interactions can be utilized by both students and health professionals to deliver/gain knowledge and make clinical diagnosis of oral lesions. Role play is also an educational technique which is designed to engage and motivate students in classrooms. This study aimed to compare usefulness of virtual clinical scenario and role play in learning oral pathology among second-year dental students. The students were randomly divided to one of the two groups: virtual clinical scenario group (n = 50) and role play group (n = 50). Virtual clinical scenario group was provided with virtual clinical cases of oral lesions through Google Forms whereas role play group was exposed to virtual clinical cases of oral lesions through role playing activity. Both groups underwent assessments before and after the intervention. Students' perceptions on usefulness of both techniques in terms of diagnosis, visual parameters and impact on learning were evaluated by feedback questionnaire. Data were analyzed using Statistical Package for the Social Sciences version 27.0. Wilcoxon signed-rank test was used to compare pre-test and post-test scores. Additionally, the scores and students' responses from both groups were compared using the Mann-Whitney U test. A P-value of < 0.05 was set as statistically significant. Students in both groups showed significantly higher post-test scores compared to their pre-test scores (P < 0.001). However, the role play group outperformed the virtual clinical scenario group, with a significantly higher post-test score (P = 0.04). Furthermore, feedback concerning role play was significantly higher than that for the virtual clinical scenario across multiple aspects (P < 0.05). Our findings suggest that role play emerges as the preferred method, significantly enhancing dental students' learning experiences in oral pathology.

Development of a murine model of oral carcinogenesis: an accelerated tool for biomarker and anti-tumour drug discovery.

Oral squamous cell carcinoma (OSCC) is the most common cancer in Pakistani men and the second most common cancer in women. The objective of our study was to devise a novel accelerated murine model of oral carcinogenesis that can be exploited as a tool to investigate the cancer circuitry involved in OSCC and to identify molecules of diagnostic, therapeutic and prognostic significance. A total of 40 healthy male, 6-8 weeks old, 22 ± 2 gram, Naval Medical Research Institute (NMRI) outbred strain mice were recruited in the experiment. NMRI mice are commonly used for animal experiments in various fields of biology and for drug toxicity. Of these, 25 mice underwent the oral carcinogenesis regimen via topical application of 0.5% 9,10-dimethyl-1,2-benzanthracene (DMBA) on the lower left lip for a maximum of 20 weeks and 15 mice were used as controls (without the carcinogenic regimen). Exophytic tissue masses were harvested, fixed in 10% formalin and stained with haematoxylin and eosin (H&E) for microscopic diagnosis. Additionally, the expression levels of CK 5/6, p53 and Ki-67 were investigated using immunohistochemistry. Of the 25 mice which underwent the carcinogenic regimen, 21 developed moderately differentiated squamous cell carcinoma and 1 showed dysplastic features with foci of invasion. Three mice were found dead with lesion(s). CK 5/6 showed strong positivity (100%) and p53 and Ki-67 showed patchy (<30%) strong positivity in OSCC, suggesting the similarity of our model to human OSCC. We present an accelerated, close-to-human carcinogenesis, model of oral carcinogenesis using DMBA in NMRI mice that can be exploited to study the pathogenesis of oral squamous cell carcinoma and subsequently devise immunotherapy or targeted therapy.

Lip and oral cavity cancers (C00-C06) from a mega city of Pakistan: Ten-year data from the Dow Cancer Registry.

OBJECTIVE: The objective of this report is to provide an overview of lip and oral cavity cancer in Karachi, the largest city in Pakistan. METHODS: This study was undertaken at the Dow Cancer Registry. During 2010-2019, all patients who were residents of Karachi who had been diagnosed with lip and oral cavity cancer were registered and recruited for this study. The data were entered in SPSS and MS Excel sheets to investigate frequencies, age-standardized-rates (ASR) and other clinicopathological parameters. The data from our study were compared with the ASR of lip and oral cavity cancer from selected Asian countries. RESULTS: During the defined period, 22,858 cancer cases were registered. Of these, 4,400 (19.2%, ASR 28.0) were lip and oral cavity cancer (the most common type found in males and the second most common type in females), of which 2,986 (67.8%) were found in males, while 1,414 (32.1%) were reported in females. Squamous cell carcinoma was the most common type (97.7%). Most tumours were moderately differentiated (67.7%) followed by poorly (16.6%), and well differentiated (15.7%). CONCLUSION: We report an alarmingly high ASR of lip and oral cavity cancer in Karachi as compared to Pakistan as a whole and other Asian countries.

Pan-Cancer Multiomics Analysis of TC2N Gene Suggests its Important Role(s) in Tumourigenesis of Many Cancers.

BACKGROUND: Role of TC2N in carcinogenesis has been largely unfathomed until recently when it was identified as a novel oncogene in lung cancer. Subsequently, a tumour suppressor role of TC2N was reported in breast cancer. It is therefore highly relevant to investigate TC2N molecular partners/mechanisms on a larger scale including a wider range of tumour types. METHODS: We investigated TC2N mRNA expression, its promoter methylation levels, effects of TC2N transcription on overall patient survival, somatic mutations in TC2N gene and correlation between TC2N mRNA expression and other cancer genes in pan-cancer by using data available from the Cancer Genome Atlas (TCGA) and the Genotype Tissue Expression (GTEx) databases. RESULTS: TC2N mRNA expression was differentially regulated in 9/33 TCGA tumour types. Of these 9 tumours, 5 tumour types (cholangiocarcinoma, ovarian-serous-cystadenocarcinoma, rectal-adenocarcinoma, stomach-adenocarcinoma and thymoma) had significantly higher TC2N mRNA expression while 4 (pheochromocytoma-and-paraganglioma, skin-cutaneous-melanoma, thyroid-carcinoma and uterine-carcinosarcoma) had significantly lower TC2N mRNA expression compared to matched and normal controls. TC2N promoter was hypermethylated in most cancers while hypomethylated in head-and-neck-squamous-cell-carcinoma and kidney-renal-clear-cell carcinoma. TC2N transcription was positively correlated with transcription of several other cancer genes including genes from Myc, cell-cycle, Nrf2, Wnt, PI3K, Hippo, Notch, TGFß and RAS/RTK pathways. Poor prognosis was associated with higher TC2N mRNA levels in pancreatic-adenocarcinoma and brain-lower-grade-glioma and lower TC2N mRNA levels in kidney-renal-clear-cell-carcinoma, mesothelioma, sarcoma and skin-cutaneous melanoma. Functional protein partners of TC2N were identified as STX2, SMEK1, SMEK2, STXBP5, SCARA5, MMRN1, CATSPER2, CATSPERB, CLEC4M and STAB2. Many of these proteins are key players in carcinogenesis of various cancers. Highest pathogenic somatic mutation rates in TC2N were found in skin-cutaneous-melanoma, uterine-corpus-endometrial-carcinoma, colon-endocervical-adenocarcinoma, bladder-urothelial-carcinoma and breast-invasive-carcinoma. CONCLUSION: Our findings unravel several un-explored avenues related to the role of TC2N in tumourigenesis of several cancers, suggesting TC2N as an important player and a potential candidate for tumour-therapy.