ABSTRACT
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.
ABSTRACT
This study was conducted to determine the various socio-demographic, economic, and clinical variables (SDECVs) which influence the health-related quality of life (HRQoL) of hypertensive patients. Three hundred and fifty hypertensive patients participated in this study through a structured questionnaire and EQ 5D 5L. 211(60.28%) participants had stage 1, and 139 (39.7%) had stage 2 hypertension. No participants reported severe problems in any domain on EQ 5D 5L. Generalize Linear Model (GLM) was used to assess the association between HRQoL and SDECVs. The mean utility and VAS score was 0.64 (±0.15) and 63.17 (±11.01) respectively. The participants of the stage 1 hypertension group had a significantly better score on each domain of EQ 5D 5L as compared to stage 1 (0.027, 0.010, 0.00, 0.00, 0.048). No participant in either group reported extreme problems in any domain. Among socio-demographic factors, the males, non-smokers, income sharing, and healthy normal hypertensive patients had better HRQoL (0.009, 0.016, 0.019, and 0.003). A lower cost of treatment was also associated with better HRQoL (0.017). Among clinical variables, stage 1 hypertension had better HRQoL than stage 2(0.035). The number of prescribed antihypertensive drugs had no effect on the quality of life (0.253), however, the non-pharmacologic interventions such as reduction in salt and oil consumption (0.035), reduction in beverages consumption (0.0014) and increased water intake (0.010) had resulted in better QoL. The patients who reported dizziness had poor HRQoL while patients who had cardiac problems and diabetes reported a significantly lower EQ-VAS score. The effect of gender on the HRQoL of hypertensive patients who had comorbid conditions was significant in the case of renal, respiratory, visual problems, and dizziness where females had a lesser utility score than males. The study reports on significant determinants which should be taken into account in an attempt to improve the health-related quality of life of hypertensive patients.
Subject(s)
Hypertension , Quality of Life , Algorithms , Cross-Sectional Studies , Dizziness , Female , Health Status , Humans , Hypertension/epidemiology , Male , Surveys and QuestionnairesABSTRACT
OBJECTIVES: To investigate immune cell densities in tumor microenvironment of hepatocellular carcinoma. METHODS: This cross-sectional study was conducted during 2017-2019 at the Dow University of Health Sciences Karachi. A total of 42 subsequent patients undergoing liver biopsy/resection and diagnosed with hepatocellular carcinoma were included in the study. Moreover, a total of 10 control tissues were also included. In order to investigate immune cells densities in hepatocellular carcinoma, immunohistochemistry was performed using antibodies including α-MPO(neutrophils), α-CD-68(macrophages), α-CD-3(T-cells), α-CD-20(B-cells), α-CD-4(CD4+ T-cells) and α-CD-8(CD8+ T-cells). Quantification of immune cells/mm2 was performed as per the College of American Pathologists' guidelines. Data were analyzed using SPSS version 21. A p-value of 0.05 was considered significant at all times. RESULTS: We report significantly increased infiltration of macrophages (mean macrophages= 306.57/mm2, p-value <0.05), moderately significant infiltration of neutrophils (p-value=0.06) and B-cells (p-value=0.07) while no significant infiltration of CD4+T-cells (p- value=0.31), and CD8+T-cells (p-value=0.39) in tumour microenvironment of patients with hepatocellular carcinoma. CONCLUSION: We provide evidence for increased macrophage infiltration in liver cancer microenvironment suggesting a potential role of these cells in hepatocarcinogenesis.
