Publications by authors named "Srinivasan Alagarsamy"

Coronavirus disease 2019 (COVID-19) is caused by the newly emerged human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the highly contagious nature of SARS-CoV-2, it has infected more than 137 million individuals and caused more than 2.9 million deaths globally as of April 13, 2021.

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Prostate-specific antigen (PSA) screening for prostate cancer (PCa) is limited by the lack of specificity but is further complicated in the benign prostatic hyperplasia (BPH) population which also exhibit elevated PSA, representing a clear unmet need to distinguish BPH from PCa. Herein, we evaluated the utility of FLNA IP-MRM, age, and prostate volume to stratify men with BPH from those with PCa. Diagnostic performance of the biomarker panel was better than PSA alone in discriminating patients with negative biopsy from those with PCa, as well as those who have had multiple prior biopsies (AUC 0.

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The causative agent of the ongoing pandemic in the world is SARS-CoV-2. The research on SARS-CoV-2 has progressed with lightning speed on various fronts, including clinical research and treatment, virology, epidemiology, drug development, and vaccine research. Recent studies reported that sera from healthy individuals, who were confirmed negative for SARS-CoV-2 by RT-PCR method, tested positive for antibodies against spike and nucleocapsid proteins of SARS-CoV-2.

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A new pandemic is ongoing in several parts of the world. The agent responsible is the newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The symptoms associated with this virus are known as the coronavirus disease-2019 (COVID-19).

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Prostate cancer is a prevalent cancer in men and consists of both indolent and aggressive phenotypes. While active surveillance is recommended for the former, current treatments for the latter include surgery, radiation, chemo and hormonal therapy. It has been observed that the recurrence in the treated patients is high and results in castration resistant prostate cancer for which treatment options are limited.

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ANXA2 (Annexin A2 or Annexin II) is a calcium dependent phospholipid binding protein with diverse cellular functions. While ANXA2 is either absent or expressed focally in the prostate epithelium of well and moderately differentiated tumours, it is highly expressed in a subset of poorly differentiated tumours. Here we examined the association between ANXA2 expression and tumour progression, with consideration of ERG expression status and patient race (Caucasian American and African American).

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The identification of prostate transmembrane protein androgen induced 1 (), an androgen responsive gene, came initially from the studies of androgen regulatory gene networks in prostate cancer. It was soon followed by the documentation of the expression and functional analysis of transmembrane prostate androgen-induced protein ()/ in other solid tumors including renal, colon, breast, lung, and ovarian cancers. Further elucidation of gene expression and sequence analysis revealed the presence of five isoforms with distinct extracellular domains (isoforms , , , , and ).

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Prostate cancer is a disease with heterogeneity of multiple gene transcriptomes and biological signaling pathways involved in tumor development. The prostate transmembrane protein, androgen induced 1 (), a multifunctional protein played critical roles in prostate tumorigenesis. The pleiotropic nature of in modulating androgen and TGF-β signaling as well as splice variants mechanisms for functional regulations of cancer-associated genes prompted us to investigate the biological roles of isoforms in prostate cancer.

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Background: Predicting the clinical course of prostate cancer is challenging due to the wide biological spectrum of the disease. The objective of our study was to identify prostate cancer prognostic markers in patients 'sera using a multi-omics discovery platform.

Methods: Pre-surgical serum samples collected from a longitudinal, racially diverse, prostate cancer patient cohort (N = 382) were examined.

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Dysfunctions of androgen/TGF-β signaling play important roles in prostate tumorigenesis. Prostate Transmembrane Protein Androgen Induced 1 () inhibits androgen and TGF-β signaling via a negative feedback loop. The loss of confers resistance to androgen signaling inhibitors and promotes bone metastasis.

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Tenascin C (TNC), an extra-cellular matrix (ECM) family gene, is expressed in several cancer tissues of breast, lung, colon, and gastrointestinal tract leading to proliferation, migration, invasion, angiogenesis and metastasis, but its role in tumorigenesis of prostate cancer is poorly understood. We took a meta-analysis approach to characterize the alterations of TNC gene in prostate cancer using publicly available databases (cBioportal Version 2.2.

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Article Synopsis
  • Prostate cancer is complex and can vary widely in how it affects patients, with some cases progressing while others remain stable, emphasizing the need for better early-stage biomarkers to predict disease outcomes.
  • A study analyzed tissue samples from prostate cancer patients who had low-risk tumors and tracked their progression, using gene expression analysis to identify differences between those who remained stable and those who developed recurring disease.
  • The research identified a set of eight genes, particularly highlighting ERG as a strong predictor of disease recurrence, indicating that these biomarkers could help in assessing prostate cancer progression from early tissue samples.
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Background: Ectatic coronary segments are nidi for thrombus formation due to altered flow dynamics and stasis-an important component of Virchow's triad. Ectasia accompanied by an adjacent coronary stenosis with or without a plaque event can lead to acute myocardial infarctions complicated by huge thrombus burden.

Case Summary: Here, we present a case of a young male with acute inferior wall myocardial infarction complicated by Type IV coronary artery ectasia of the right coronary artery and huge thrombus burden that was refractory to conventional methods of thrombus management like thrombo-suction and intracoronary cocktails including tenecteplase.

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The oncogenic activation of the ETS-related gene () due to gene fusions is present in over half of prostate cancers in Western countries. Because of its high incidence and oncogenic role, ERG and components of ERG network have emerged as potential drug targets for prostate cancer. Utilizing gene expression datasets, from matched normal and prostate tumor epithelial cells, an association of NOTCH transcription factors with expression status was identified, confirming that factors are direct transcriptional targets of ERG.

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Article Synopsis
  • Overdiagnosis and overtreatment of prostate cancer (CaP) in the U.S. is largely due to reliance on PSA screening, prompting the search for better diagnostic biomarkers.
  • Researchers investigated the presence of autoantibodies (AAbs) against the ERG oncoprotein in CaP patients and found significantly higher levels in their blood compared to healthy individuals.
  • The study suggests that a panel of AAbs including anti-ERG, AMACR, and HERV-K Gag could effectively differentiate CaP patients from healthy controls, indicating their potential as useful biomarkers for diagnosis and prognosis.
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Background: The established methods for detecting prostate cancer (CaP) are based on tests using PSA (blood), PCA3 (urine), and AMACR (tissue) as biomarkers in patient samples. The demonstration of ERG oncoprotein overexpression due to gene fusion in CaP has thus provided ERG as an additional biomarker. Based on this, we hypothesized that ERG protein quantification methods can be of use in the diagnosis of prostate cancer.

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The fusion between ERG coding sequences and the TMPRSS2 promoter is the most prevalent in prostate cancer (CaP). The presence of two main types of TMPRSS2-ERG fusion transcripts in CaP specimens, Type I and Type II, prompted us to hypothesize that the cumulative actions of different ERG variants may impact CaP development/progression. Using TMPRSS2-ERG3 (Type I) and TMPRSS2-ERG8 (Type II) expression vectors, we determined that the TMPRSS2- ERG8 encoded protein is deficient in transcriptional regulation compared to TMPRSS2-ERG3.

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Recently we reported the development of a highly specific murine monoclonal antibody (ERG MAb 9FY) against the ERG oncoprotein. ERG is expressed in over half of all prostate cancers (CaP) as a result of specific gene fusions involving ERG and the androgen regulated TMPRSS2 promoter. ERG MAb 9FY has been extensively used in the evaluations of CaP.

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The architecture of nanoparticles of biological origin, generally also known as bionanoparticles, presents several features that are ideal for their use in developing diagnostics, therapeutics, and vaccines. In this regard, particles formed by viral proteins using recombinant DNA technology resemble authentic virus particles. However, they lack infectivity due to the absence of genetic components such as DNA or RNA.

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The prostate transmembrane protein androgen induced 1 (PMEPA1) gene is highly expressed in prostate epithelial cells and is a direct transcriptional target for the androgen receptor (AR). AR protein levels are controlled by the AR-PMEPA1 negative feedback loop through NEDD4-E3 ligase. Reduced expression of PMEPA1 observed in prostate tumors, suggests that loss of PMEPA1 may play critical roles in prostate tumorigenesis.

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Following infection with Human immunodeficiency virus 1 (HIV-1) there is a remarkable variation in virus replication and disease progression. Both host and viral factors have been implicated in the observed differences in disease status. Here, we focus on understanding the contribution of HIV-1 viral protein R (Vpr) by evaluating the disease-associated Vpr polymorphism and its biological functions from HIV-1 positive rapid progressor (RP) and long-term nonprogressor (LTNP) subjects.

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Background: Human immunodeficiency virus type 1 (HIV-1) induces neuronal dysfunction through host cellular factors and viral proteins including viral protein R (Vpr) released from infected macrophages/microglia. Vpr is important for infection of terminally differentiated cells such as macrophages. The objective of this study was to assess the effect of Vpr in the context of infectious virus particles on neuronal death through proinflammatory cytokines released from macrophages.

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HIV-1 Vpr, a nonstructural viral protein associated with virus particles, has a positive role in the efficient transport of PIC into the nucleus of non-dividing target cells and enhances virus replication in primary T cells. Vpr is a 96 amino acid protein and the structure by NMR shows three helical domains. Vpr has been shown to exist as dimers and higher order oligomers.

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