Oral squamous cell carcinoma (OSCC) progresses from preneoplastic precursors via genetic and epigenetic alterations. Previous studies have focused on the treatment of terminally developed OSCC. However, the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied. Our study identified lysine-specific demethylase 1 (LSD1) as a crucial promoter of OSCC, demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia. LSD1 inhibition by SP2509 disrupted cell cycle, reduced immunosuppression, and enhanced CD4+ and CD8+ T-cell infiltration. In a feline model of spontaneous OSCC, a clinical LSD1 inhibitor (Seclidemstat or SP2577) was found to be safe and effectively inhibit the STAT3 network. Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling, which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4. Notably, LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422, offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition. This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.
STAT3 Transcription Factor/metabolism* ; Animals ; Histone Demethylases/genetics* ; Phosphorylation ; Mouth Neoplasms/immunology* ; Mice ; Carcinoma, Squamous Cell/immunology* ; Disease Progression ; Cyclin-Dependent Kinase-Activating Kinase ; Precancerous Conditions/metabolism* ; Humans ; Cyclin-Dependent Kinases/metabolism* ; Disease Models, Animal

Background/Aims: A Helicobacter pylori (H. pylori) infection is the most common cause of chronic gastritis (CG), with approximately 50% of the world’s population infected. Long-term infection increases the risk of progression to gastric cancer. This study evaluated the histopathological changes in CG using the Updated Sydney System (USS) to estimate the prevalence and correlation of H. pylori gastritis with other histological variables. Methods: This research was a prospective observational study conducted in the Department of Pathology of a tertiary care teaching hospital in Central India. The study was conducted between Feb 2017 to April 2018. Two antral biopsies were taken per patient, one for a Rapid Urease Test and the second for routine histopathology. All samples were analyzed according to the USS. Results: CG was found in 83.84% of total dyspeptic patients. The most common age group was 31–40 years, with a male preponderance. Of 109 gastric antral biopsies with histopathological evidence of chronic gastritis, neutrophilic activity, intestinal metaplasia, atrophy, and lymphoid aggregates were present in 50 (45.87%), 10 (9.2%), 23 (21.10%), and 11(10.09%) cases, respectively.The prevalence of H. pylori was 46.78%, and its association with the degree of chronic inflammation and intestinal metaplasia was statistically significant. Conclusions H. pylori was significantly associated with the degree of chronic inflammation and intestinal metaplasia. Hence, this study suggests a vigorous search for H. pylori should be initiated if chronic inflammation and intestinal metaplasia are seen in antral gastric biopsies.

Background/Aims: A Helicobacter pylori (H. pylori) infection is the most common cause of chronic gastritis (CG), with approximately 50% of the world’s population infected. Long-term infection increases the risk of progression to gastric cancer. This study evaluated the histopathological changes in CG using the Updated Sydney System (USS) to estimate the prevalence and correlation of H. pylori gastritis with other histological variables. Methods: This research was a prospective observational study conducted in the Department of Pathology of a tertiary care teaching hospital in Central India. The study was conducted between Feb 2017 to April 2018. Two antral biopsies were taken per patient, one for a Rapid Urease Test and the second for routine histopathology. All samples were analyzed according to the USS. Results: CG was found in 83.84% of total dyspeptic patients. The most common age group was 31–40 years, with a male preponderance. Of 109 gastric antral biopsies with histopathological evidence of chronic gastritis, neutrophilic activity, intestinal metaplasia, atrophy, and lymphoid aggregates were present in 50 (45.87%), 10 (9.2%), 23 (21.10%), and 11(10.09%) cases, respectively.The prevalence of H. pylori was 46.78%, and its association with the degree of chronic inflammation and intestinal metaplasia was statistically significant. Conclusions H. pylori was significantly associated with the degree of chronic inflammation and intestinal metaplasia. Hence, this study suggests a vigorous search for H. pylori should be initiated if chronic inflammation and intestinal metaplasia are seen in antral gastric biopsies.

Background/Aims: A Helicobacter pylori (H. pylori) infection is the most common cause of chronic gastritis (CG), with approximately 50% of the world’s population infected. Long-term infection increases the risk of progression to gastric cancer. This study evaluated the histopathological changes in CG using the Updated Sydney System (USS) to estimate the prevalence and correlation of H. pylori gastritis with other histological variables. Methods: This research was a prospective observational study conducted in the Department of Pathology of a tertiary care teaching hospital in Central India. The study was conducted between Feb 2017 to April 2018. Two antral biopsies were taken per patient, one for a Rapid Urease Test and the second for routine histopathology. All samples were analyzed according to the USS. Results: CG was found in 83.84% of total dyspeptic patients. The most common age group was 31–40 years, with a male preponderance. Of 109 gastric antral biopsies with histopathological evidence of chronic gastritis, neutrophilic activity, intestinal metaplasia, atrophy, and lymphoid aggregates were present in 50 (45.87%), 10 (9.2%), 23 (21.10%), and 11(10.09%) cases, respectively.The prevalence of H. pylori was 46.78%, and its association with the degree of chronic inflammation and intestinal metaplasia was statistically significant. Conclusions H. pylori was significantly associated with the degree of chronic inflammation and intestinal metaplasia. Hence, this study suggests a vigorous search for H. pylori should be initiated if chronic inflammation and intestinal metaplasia are seen in antral gastric biopsies.

Background/Aims: A Helicobacter pylori (H. pylori) infection is the most common cause of chronic gastritis (CG), with approximately 50% of the world’s population infected. Long-term infection increases the risk of progression to gastric cancer. This study evaluated the histopathological changes in CG using the Updated Sydney System (USS) to estimate the prevalence and correlation of H. pylori gastritis with other histological variables. Methods: This research was a prospective observational study conducted in the Department of Pathology of a tertiary care teaching hospital in Central India. The study was conducted between Feb 2017 to April 2018. Two antral biopsies were taken per patient, one for a Rapid Urease Test and the second for routine histopathology. All samples were analyzed according to the USS. Results: CG was found in 83.84% of total dyspeptic patients. The most common age group was 31–40 years, with a male preponderance. Of 109 gastric antral biopsies with histopathological evidence of chronic gastritis, neutrophilic activity, intestinal metaplasia, atrophy, and lymphoid aggregates were present in 50 (45.87%), 10 (9.2%), 23 (21.10%), and 11(10.09%) cases, respectively.The prevalence of H. pylori was 46.78%, and its association with the degree of chronic inflammation and intestinal metaplasia was statistically significant. Conclusions H. pylori was significantly associated with the degree of chronic inflammation and intestinal metaplasia. Hence, this study suggests a vigorous search for H. pylori should be initiated if chronic inflammation and intestinal metaplasia are seen in antral gastric biopsies.

Background/Aims: A Helicobacter pylori (H. pylori) infection is the most common cause of chronic gastritis (CG), with approximately 50% of the world’s population infected. Long-term infection increases the risk of progression to gastric cancer. This study evaluated the histopathological changes in CG using the Updated Sydney System (USS) to estimate the prevalence and correlation of H. pylori gastritis with other histological variables. Methods: This research was a prospective observational study conducted in the Department of Pathology of a tertiary care teaching hospital in Central India. The study was conducted between Feb 2017 to April 2018. Two antral biopsies were taken per patient, one for a Rapid Urease Test and the second for routine histopathology. All samples were analyzed according to the USS. Results: CG was found in 83.84% of total dyspeptic patients. The most common age group was 31–40 years, with a male preponderance. Of 109 gastric antral biopsies with histopathological evidence of chronic gastritis, neutrophilic activity, intestinal metaplasia, atrophy, and lymphoid aggregates were present in 50 (45.87%), 10 (9.2%), 23 (21.10%), and 11(10.09%) cases, respectively.The prevalence of H. pylori was 46.78%, and its association with the degree of chronic inflammation and intestinal metaplasia was statistically significant. Conclusions H. pylori was significantly associated with the degree of chronic inflammation and intestinal metaplasia. Hence, this study suggests a vigorous search for H. pylori should be initiated if chronic inflammation and intestinal metaplasia are seen in antral gastric biopsies.