Objectives Gold nanoparticles (AuNPs) are used to deliver drugs and therapeutic small molecule inhibitors to cancer cells. Evidence shows that AuNPs coated with nuclear localization sequence can cross the nuclear membrane and induce cellular apoptosis. To determine the therapeutic role of AuNPs, we compared two nanoconstructs conjugated to doxorubicin (DOX) through pH‐sensitive and pH‐resistant linkers. Materials and Methods We tested DOX nanoconjugates' cytotoxicity, cellular and nuclear uptake in oral squamous cell carcinoma cell line. Furthermore, we evaluated the therapeutic effect of pH‐sensitive and pH‐resistant DOX bioconjugates in hamster buccal pouch carcinoma model. Results Our data indicate that pH‐resistant and pH‐sensitive DOX‐nanoconjugates were equally localized in cancer cells, but the pH‐resistant DOX nanoparticles were more localized in the nuclei inducing a 2‐fold increase in the apoptotic effect compared with the pH‐sensitive DOX nanoparticles. Our in vivo results show significantly higher tumor shrinkage and survival rates in animals treated with DOX pH‐resistant AuNPs compared with pH‐sensitive ones. Conclusion Our findings suggest that AuNPs enhance the cytotoxic effect against cancer cells in addition to acting as drug carriers. DOX pH‐resistant AuNPs enhanced accumulation of AuNPs in cancer cells’ nuclei inducing a significant cellular apoptosis which was confirmed using in vitro and in vivo experiments without deleterious effects on blood cell count.
INTRODUCTION:Oral potentially malignant disorders (OPMDs) describe mucosal disorders with an increased risk of malignant transformation (MT) to oral squamous cell carcinoma (OSCC). Natural products like garlic represent a promising group of chemopreventive agents. Aged garlic extract (AGE) is one of the most commonly used garlic preparations as it contains more stable organosulfur compounds (OSCs); S-allylcysteine (SAC) is the most abundant organosulfur compound in AGE. SAC has been found to retard the growth of chemically induced and transplantable tumors in several animal models. OBJECTIVES: To evaluate the cancer chemopreventive effect of topically applied S-Allylcysteine in the management of oral dysplastic potentially malignant disorders. MATERIALS AND METHODS:10 subjects with oral dysplastic potentially malignant disorders, as proven clinically and histopathologically, were recruited for this study. They received topical S-Allylcysteine for 1 month, and then the lesions were evaluated both clinically and histopathologically after termination of therapy to assess any alterations in the lesions' size, pain score and mucosal dysplasia. RESULTS: S-allylcysteine was well tolerated by all the patients. After termination of the therapeutic phase (after one month), S-Allylcysteine was found to decrease the pain score in all symptomatic patients. The size of the lesions was also decreased although it was not statistically significant; however, histological improvement was remarkable. Complete histological response was observed in four leukoplakia patients and two lichen planus patients where the mild and moderate dysplastic changes showed histologic remission of dysplasia. However, two leukoplakia cases showed progression in the grade of dysplasia from mild to moderate. CONCLUSIONS: Topical application of S-Allylcysteine is beneficial for the management of dysplasia associated with oral potentially malignant disorders.
BackgroundHead and neck cancer is a major health problem. Recent studies on the pathobiology of oral squamous cell carcinoma (OSCC) have led to the discovery of a small population of cancer cells with a consistent behavior with the features of cancer stem cells (CSCs). CSCs are required and responsible for initiation, maintenance and recurrence of disease. Molecular markers are commonly used for the identification of CSCs. CD44 is the most reported CSC marker in OSCC.The aim of the study was to evaluate and correlate the expression of CD44 in different histopathological grades of OSCC, as well as to assess the diagnostic and prognostic value of soluble CD44 (CD44sol) in peripheral blood of patients.Materials and methodsFifteen patients with OSCC were included; biopsies were histologically evaluated using haematoxylin and eosin. Serial sections were immunohistochemically stained by monoclonal antibody to CD44. The intensity of immunostaining of CD44 was calculated. Enzyme-linked immunosorbent assay (ELISA) method was used to determine the concentration of CD44sol in the blood serum.ResultsAll grades of OSCC showed membranous immunosignaling of CD44. The well, moderately and poorly differentiated OSCC cases showed weak, moderate and intense positive membranous immunosignaling of CD44 respectively.CD44sol levels were significantly higher in OSCC patients than they were in control groups. Soluble CD44 serum levels were significantly higher in poorly differentiated than they were in moderately and well differentiated.ConclusionCSCs detection in fixed human tissue and CD44sol detection in peripheral blood using ELISA seemed to be a promising method and may have a diagnostic and prognostic value in management of OSCC.
Rhabdomyoblastic differentiation in a malignant peripheral nerve sheath tumor (MPNST) is termed malignant triton tumor (MTT), a rare neoplasm that poses a diagnostic dilemma in the differential diagnosis of neck masses and portends poor prognosis. We report a sporadic case of MTT of the neck in a 23-year-old female. We present the pathological findings. Immunohistochemistry confirmed the neurogenic origin with S-100 expression and the rhabdomyoblastic differentiation with desmin and vimentin positivity. Radical surgical excision was done. After 4 years there were no signs of recurrence or distant metastasis. The clinical, microscopic, and long-term follow-up of this case are consistent with those of a low-grade malignancy.
INTRODUCTION:Oral cancer is a major health problem, causing high morbidity and mortality rates. Oral Squamous Cell Carcinoma (OSCC) accounts for 90-95% of all oral malignancies. The prognosis of OSCC is often poor due to the late discovery of most lesions, after they have reached a large size. Here comes the role of biomarkers of genetic damage that can have excellent use in early diagnosis of cancer. Micronuclei are small extranuclear bodies formed by chromosome fragments or whole chromosomes that lag behind at anaphase and are not incorporated into the resulting daughter nuclei but are covered by a nuclear membrane and resemble a small nucleus. Many investigators have already called micronuclei (MN) an upcoming biomarker of tumorogenesis. More than 90% of human malignancies originate from epithelial cells. Thus the MN test in exfoliated buccal epithelial cells could be used as an objective, non-invasive tool for biomonitoring the genetic damage in high risk human populations and for screening cellular alteration in OSCC cases. OBJECTIVES: To assess the degree of genetic damage in the oral squamous cell carcinoma lesions using micronuclei as biomarkers. MATERIALS AND METHODS: A total of thirty four participants; seventeen OSCC patients and17 healthy control subjects were included. Cytological smears were taken from the lesion of the OSCC cases as well as from the buccal mucosa of the control group subjects using a cytobrush. Cytological smears were stained using Papanicolaou stain and the number of micronucleated (MNed) cells per 1000 cells was determined for each subject. RESULTS: There was a statistically significant difference between the number of MNed cells in the cytological smears of OSCC cases and those of the healthy control subjects. CONCLUSIONS: The number of MNed cells increases significantly in cancer patients thus they can be considered as an important biomarker for genetic damage.
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