1.Lysine-specific demethylase 1 controls key OSCC preneoplasia inducer STAT3 through CDK7 phosphorylation during oncogenic progression and immunosuppression.
Amit Kumar CHAKRABORTY ; Rajnikant Dilip RAUT ; Kisa IQBAL ; Chumki CHOUDHURY ; Thabet ALHOUSAMI ; Sami CHOGLE ; Alexa S ACOSTA ; Lana FAGMAN ; Kelly DEABOLD ; Marilia TAKADA ; Bikash SAHAY ; Vikas KUMAR ; Manish V BAIS
International Journal of Oral Science 2025;17(1):31-31
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*
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Animals
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Histone Demethylases/genetics*
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Phosphorylation
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Mouth Neoplasms/immunology*
;
Mice
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Carcinoma, Squamous Cell/immunology*
;
Disease Progression
;
Cyclin-Dependent Kinase-Activating Kinase
;
Precancerous Conditions/metabolism*
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Humans
;
Cyclin-Dependent Kinases/metabolism*
;
Disease Models, Animal
2.Optical Coherence Tomography-Guided Percutaneous Intervention: A Comparative Study
Sanjeeb ROY ; Ashwini SHARMA ; Anurodh DADARWAL ; Krishna Kumar SHARMA ; Manish NARANG ; Nick E.J. WEST
Cardiovascular Imaging Asia 2024;8(1):2-10
Objective:
Optical coherence tomography (OCT) is considered superior to coronary angiography (CA). However, OCT is not widely used, and data are limited in India. In the present study, the efficacy and safety of OCT for guiding percutaneous coronary intervention (PCI) in all-comer patients were evaluated and compared with those of CA.
Materials and Methods:
In this retrospective study, the data associated with 434 patients who underwent PCI between December 2018 and June 2020 were analyzed. The primary endpoint was major adverse cardiac events (MACEs) at 6 months.
Results:
The patients were divided into OCT-guided and angiography-guided PCI groups (217 in each group) after propensity matching. The OCT-guided PCI group had a significantly larger proportion of patients with unstable angina (55.7% vs. 43.3%, p=0.009) and non-STelevation myocardial infarction (NSTEMI; 17.5% vs. 10.0%, p=0.02) compared with the angiography-guided PCI group, and the proportion of patients with STEMI was significantly lower in the OCT-guided PCI group than in the angiography-guided PCI group (23.5% vs. 41.5%, p=0.00005). The OCT-guided PCI group had a lower incidence of MACEs at 6 months than the angiography-guided PCI group but without statistical significance (6.9% vs. 9.7%, p=0.296).Incidences of target lesion failure, target vessel myocardial infarction, in-stent restenosis, or stent thrombosis did not occur in either group. On post-PCI OCT, stent underexpansion, tissue prolapse, stent edge dissection, and stent malapposition were observed in 28.5%, 10%, 4.1%, and 3.7% of the cases, respectively.
Conclusion
When comparing OCT-guided PCI with angiography-guided PCI, OCT-guided PCI showed slightly superior clinical outcomes at 6 months, although the differences were not statistically significant.
3.An Unusual Case of BSND Gene–Related (Type IV) Bartter Syndrome Presenting as Antenatal Bartter Syndrome: A Case Report and Review of Literature
Shajan Aleena M. ; Manish KUMAR ; Preethi NAVANEETHAN ; Sumita DANDA ; Beck Manisha M.
Maternal-Fetal Medicine 2023;05(2):128-130
Bartter syndrome is a group of autosomal recessive renal tubular disorders; it has two types of presentation: antenatal and classic. The antenatal type presents as severe unexplained polyhydramnios in the second trimester. This is due to fetal urinary losses of sodium, chloride, and potassium, leading to fetal polyuria. The classic type presents in the late neonatal or infancy stage, with dehydration, dyselectrolytemia, failure to thrive, and nephrocalcinosis. Antenatal scans are normal in such cases. Type I and II Bartter syndrome presents in the antenatal period, whereas type IV has a classic presentation. We describe an unusual case of type IVa Bartter syndrome presenting in the antenatal period, with severe polyhydramnios. The initial diagnosis was made based on amniotic fluid chloride levels and later confirmed by performing a genetic test. Genetic testing is important for confirming diagnosis and prognostication regarding the condition.
4.An Unusual Case of BSND Gene–Related (Type IV) Bartter Syndrome Presenting as Antenatal Bartter Syndrome: A Case Report and Review of Literature
Shajan Aleena M. ; Manish KUMAR ; Preethi NAVANEETHAN ; Sumita DANDA ; Beck Manisha M.
Maternal-Fetal Medicine 2023;05(2):128-130
Bartter syndrome is a group of autosomal recessive renal tubular disorders; it has two types of presentation: antenatal and classic. The antenatal type presents as severe unexplained polyhydramnios in the second trimester. This is due to fetal urinary losses of sodium, chloride, and potassium, leading to fetal polyuria. The classic type presents in the late neonatal or infancy stage, with dehydration, dyselectrolytemia, failure to thrive, and nephrocalcinosis. Antenatal scans are normal in such cases. Type I and II Bartter syndrome presents in the antenatal period, whereas type IV has a classic presentation. We describe an unusual case of type IVa Bartter syndrome presenting in the antenatal period, with severe polyhydramnios. The initial diagnosis was made based on amniotic fluid chloride levels and later confirmed by performing a genetic test. Genetic testing is important for confirming diagnosis and prognostication regarding the condition.
5.Preventable iatrogenic cause of foot-drop in knee injuries with literature review
Anant KRISHNA ; Sumit ARORA ; Rakesh GOYAL ; Manish KUMAR ; Nirup NAIK ; Manoj KUMAR
Chinese Journal of Traumatology 2022;25(4):224-231
Purpose::Common peroneal nerve palsy is quite disabling and every effort should be made to prevent its injury during the treatment.Methods::We retrospectively reviewed the prospectively collected data of 7 cases of tibial plateau fractures in association with proximal fibula fracture from January 2019 to September 2019 who presented to emergency room of our hospital.Results::In addition to fibular neck fracture, the first case had type 6 tibial plateau displaced fracture and the second case had displaced acetabular fracture with instability of knee with tibial tuberosity avulsion. common peroneal nerve palsy developed following application of distal tibial skeletal traction in both the cases. Other 6 such cases remained neurologically intact as traction was not applied to them.Conclusion::Such iatrogenic complication could have been prevented if the injury pattern of "concomitant medial and lateral columns" of the proximal leg is kept in mind by the treating surgeon before applying skeletal traction.
6.Primary pulmonary epithelioid inflammatory myofibroblastic sarcoma: a rare entity and a literature review
Priyanka SINGH ; Aruna NAMBIRAJAN ; Manish Kumar GAUR ; Rahul RAJ ; Sunil KUMAR ; Prabhat Singh MALIK ; Deepali JAIN
Journal of Pathology and Translational Medicine 2022;56(4):231-237
Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumor (IMT) harboring anaplastic lymphoma kinase (ALK) gene fusions and is associated with high risk of local recurrence and poor prognosis. Herein, we present a young, non-smoking male who presented with complaints of cough and dyspnoea and was found to harbor a large right lower lobe lung mass. Biopsy showed a high-grade epithelioid to rhabdoid tumor with ALK and desmin protein expression. The patient initially received 5 cycles of crizotinib and remained stable for 1 year; however, he then developed multiple bony metastases, for which complete surgical resection was performed. Histopathology confirmed the diagnosis of EIMS, with ALK gene rearrangement demonstrated by fluorescence in situ hybridization. Postoperatively, the patient is asymptomatic with stable metastatic disease on crizotinib and has been started on palliative radiotherapy. EIMS is a very rare subtype of IMT that needs to be included in the differential diagnosis of ALKexpressing lung malignancies in young adults.
7.Development of a Unique Mouse Intervertebral Disc Degeneration Model Using a Simple Novel Tool
Manish BALDIA ; Sunithi MANI ; Noel WALTER ; Sanjay KUMAR ; Alok SRIVASTAVA ; Krishna PRABHU
Asian Spine Journal 2021;15(4):415-423
Methods:
A total of 18 mice were divided into injured (n=12) and non-injured (n=6) groups. The disc height index (DHI%) at coccygeal 4–5 level was measured by computed tomography (CT) scan for all mice. Coccygeal 4–5 discs of the injury group were injured using a 32G needle fixed to a novel tool and confirmed by CT. The non-injury group underwent no procedure. DHI% was measured by CT at 2-, 4-, and 6-week post-injury, and all mice tails were sectioned for histopathology grading of disc degeneration at the respective time intervals.
Results:
The injured group showed significant variation in DHI% at 2, 4, and 6 weeks, whereas there was no change in the noninjured group. Histopathologic evaluation with Safranin O stain showed a worsening of the disc degeneration score at 2, 4, and 6 weeks in the injured group, but in the non-injured group there was no change. Percutaneous needle injury technique with our novel tool provided 100% accuracy and uniform degeneration.
Conclusions
A simple, easily reproducible mouse model for disc degeneration was created using a simple, cost-effective, novel tool and technique, its advantage being high precision and user friendly.
8.COVID-19 Rapid Antigen Test: Role in Screening Prior to Gastrointestinal Endoscopy
Ashok DALAL ; Ujjwal SONIKA ; Manish KUMAR ; Roshan GEORGE ; Ajay KUMAR ; Siddharth SRIVASTAVA ; Sanjeev SACHDEVA ; Barjesh Chander SHARMA
Clinical Endoscopy 2021;54(4):522-525
Background/Aims:
The severe acute respiratory syndrome coronavirus 2 pandemic has affected the gastrointestinal (GI) endoscopy units globally owing to the risk of transmission. We present our data on the use of rapid antigen test (RAT) as a screening tool prior to endoscopy to prevent the transmission of coronavirus disease (COVID-19).
Methods:
This study was a retrospective analysis of patients who underwent any GI endoscopic procedure from July 2020 to October 2020 at a tertiary referral center in New Delhi, India. All patients underwent screening for COVID-19 using RAT, and endoscopy was performed only when the RAT was negative. The data are presented as numbers and percentages.
Results:
A total of 3,002 endoscopic procedures were performed during the study period. Only one endoscopic procedure was performed in a COVID-19 positive patient. A total of 53 healthcare workers were involved in conducting these procedures. Only 2 healthcare workers (3.8%) were diagnosed COVID-19 positive, presumably due to community-acquired infection, during this period.
Conclusions
The COVID-19 RAT is easily usable as a simple screening tool prior to GI endoscopy during the COVID-19 pandemic.
9.Development of a Unique Mouse Intervertebral Disc Degeneration Model Using a Simple Novel Tool
Manish BALDIA ; Sunithi MANI ; Noel WALTER ; Sanjay KUMAR ; Alok SRIVASTAVA ; Krishna PRABHU
Asian Spine Journal 2021;15(4):415-423
Methods:
A total of 18 mice were divided into injured (n=12) and non-injured (n=6) groups. The disc height index (DHI%) at coccygeal 4–5 level was measured by computed tomography (CT) scan for all mice. Coccygeal 4–5 discs of the injury group were injured using a 32G needle fixed to a novel tool and confirmed by CT. The non-injury group underwent no procedure. DHI% was measured by CT at 2-, 4-, and 6-week post-injury, and all mice tails were sectioned for histopathology grading of disc degeneration at the respective time intervals.
Results:
The injured group showed significant variation in DHI% at 2, 4, and 6 weeks, whereas there was no change in the noninjured group. Histopathologic evaluation with Safranin O stain showed a worsening of the disc degeneration score at 2, 4, and 6 weeks in the injured group, but in the non-injured group there was no change. Percutaneous needle injury technique with our novel tool provided 100% accuracy and uniform degeneration.
Conclusions
A simple, easily reproducible mouse model for disc degeneration was created using a simple, cost-effective, novel tool and technique, its advantage being high precision and user friendly.
10.COVID-19 Rapid Antigen Test: Role in Screening Prior to Gastrointestinal Endoscopy
Ashok DALAL ; Ujjwal SONIKA ; Manish KUMAR ; Roshan GEORGE ; Ajay KUMAR ; Siddharth SRIVASTAVA ; Sanjeev SACHDEVA ; Barjesh Chander SHARMA
Clinical Endoscopy 2021;54(4):522-525
Background/Aims:
The severe acute respiratory syndrome coronavirus 2 pandemic has affected the gastrointestinal (GI) endoscopy units globally owing to the risk of transmission. We present our data on the use of rapid antigen test (RAT) as a screening tool prior to endoscopy to prevent the transmission of coronavirus disease (COVID-19).
Methods:
This study was a retrospective analysis of patients who underwent any GI endoscopic procedure from July 2020 to October 2020 at a tertiary referral center in New Delhi, India. All patients underwent screening for COVID-19 using RAT, and endoscopy was performed only when the RAT was negative. The data are presented as numbers and percentages.
Results:
A total of 3,002 endoscopic procedures were performed during the study period. Only one endoscopic procedure was performed in a COVID-19 positive patient. A total of 53 healthcare workers were involved in conducting these procedures. Only 2 healthcare workers (3.8%) were diagnosed COVID-19 positive, presumably due to community-acquired infection, during this period.
Conclusions
The COVID-19 RAT is easily usable as a simple screening tool prior to GI endoscopy during the COVID-19 pandemic.

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