Elevated N1-Acetylspermidine Levels in Doxorubicin-treated MCF-7 Cancer Cells: Histone Deacetylase 10 Inhibition with an N1-Acetylspermidine Mimetic.

Cancer drug resistance is associated with metabolic adaptation. Cancer cells have been shown to implicate acetylated polyamines in adaptations during cell death. However, exploring the mimetic of acetylated polyamines as a potential anticancer drug is lacking. We performed intracellular metabolite profiling of human breast cancer MCF-7 cells treated with doxorubicin (DOX), a well known anticancer drug. A novel and in-house vertical tube gel electrophoresis assisted procedure followed by LC-HRMS analysis was employed to detect acetylated polyamines such as N1-acetylspermidine. We designed a mimetic N1-acetylspermidine (MINAS) which is a known substrate of histone deacetylase 10 (HDAC10). Molecular docking and molecular dynamics (MDs) simulations were used to evaluate the inhibitory potential of MINAS against HDAC10. The inhibitory potential and the ADMET profile of MINAS were compared to a known HDAC10 inhibitor Tubastatin A. N1-acetylspermidine, an acetylated form of polyamine, was detected intracellularly in MCF-7 cells treated with DOX over DMSO-treated MCF-7 cells. We designed and curated MINAS (PubChem CID 162679241). Molecular docking and MD simulations suggested the strong and comparable inhibitory potential of MINAS (-8.2 kcal/mol) to Tubastatin A (-8.4 kcal/mol). MINAS and Tubastatin A share similar binding sites on HDAC10, including Ser138, Ser140, Tyr183, and Cys184. Additionally, MINAS has a better ADMET profile compared to Tubastatin A, with a high MRTD value and lower toxicity. In conclusion, the data show that N1-acetylspermidine levels rise during DOX-induced breast cancer cell death. Additionally, MINAS, an N1-acetylspermidine mimetic compound, could be investigated as a potential anticancer drug when combined with chemotherapy like DOX.

Alveolar soft-part sarcoma of the oral cavity: A review of literature.

An alveolar soft-part sarcoma is a malignant neoplasm primarily affecting the soft tissues of head and neck. The aim of the present review is to systematically present the demographic and clinico-pathological data of articles published in the English medical literature. A comprehensive search of the databases (PubMed, Medline, SCOPUS, Web of Science, and Google Scholar) along with cross references to the published articles on alveolar soft-part sarcoma for eligible studies/case reports published since 1957 till date was done to retrieve the data. A total of 74 cases were identified and analyzed from 42 papers published in the English medical literature. All the clinical, radiographic, and prognostic features were analyzed and presented along with the treatment strategies. Alveolar soft-part sarcoma is a rare and aggressive malignancy of uncertain histologic origin with a propensity for vascular invasion and distant metastasis. This neoplasm requires careful clinical, radiographic, and histopathologic evaluation to reach to the correct diagnosis.

Prosthetic rehabilitation of oral submucous fibrosis patients: A systematic review of published case reports and case series.

BACKGROUND: Oral submucous fibrosis (OSF) is an insidious chronic condition characterized by restricted mouth opening. Prosthetic rehabilitation is challenging for OSF patients as obtaining a good impression requires adequate mouth opening. The aim of the present review is to systematically present the data from case reports published in the English-language literature. METHOD: A comprehensive search of the literature databases (PubMed, Medline, SCOPUS, Web of Science and Google Scholar) along with the references of published articles on prosthetic rehabilitation in OSF patients published to date was conducted. Keywords included a combination of 'Oral submucous fibrosis', 'prosthesis', 'dentures' and/or 'restricted mouth opening'. Citations from selected references and bibliographic linkages taken from similar cases were included in this review. The inclusion criteria selected for case reports on prosthetic rehabilitation in OSF patients, and cases of restricted mouth opening due to causes other than OSF were excluded from the study. RESULTS: A total of 21 cases were identified and analysed from 17 papers published in the English-language literature. Of these, 9 cases employed the sectional denture technique, 4 cases emphasized the need-based treatment approach in which conventional methods were modified, and 4 cases used mouth exercising devices. Finally, 1 case each involved, flexible denture, oral screen prosthesis, oral stents, surgery in conjunction with dentures. CONCLUSION: Prosthetic rehabilitation in OSF patients is a multifaceted approach and should be patient specific, although sectional dentures have achieved the best results.

Mucous Cell Prosoplasia in Oral Pathologies: A Brief Review.

One of the enigmas in cell differentiation process is prosoplasia, which is contemplated as forward differentiation. A well-known example of prosoplastic switch is mucous cell prosoplasia, which is the transformation of a simple squamous epithelial cell into mucous secreting cell. Numerous theories have been proposed for histogenesis of this phenomenon, which are comprehensively discussed in the present paper. Oral pathologies like odontogenic cysts and salivary gland tumours show mucous prosoplasia quite often; sometimes leading to diagnostic difficulties. In the present paper, efforts have been made to comprehensively discuss diverse aspects of mucous prosoplasia like histogenesis, theories and diagnostic importance in various oral pathologies.