Papers by Sakthivel Muniyan
American Journal of Physiology-regulatory Integrative and Comparative Physiology, Apr 1, 2023
Introduction: Hormone sensitive advanced prostate cancer (PCa) is an incurable disease that is tr... more Introduction: Hormone sensitive advanced prostate cancer (PCa) is an incurable disease that is treated with a variety of hormonal therapies targeting the androgen/androgen receptor signaling axis. For decades androgen deprivation therapy (ADT) by surgical or chemical castration is the gold standard for the treatment of advanced PCa. Areas covered: This review discusses the pharmacological features of Leuprolide, a luteinizing hormone-releasing hormone (LHRH) agonists/analog and the most commonly used drug in ADT. Expert opinion: Although Leuprolide has been on the market for more than 30 years it is still the leading option for ADT and serves as a basis for most multimodal therapy concepts. The fact that with the onset of castration-resistance in late stage metastatic disease, a prolongation of ADT in combination with a second line hormonal manipulation is recommended supports the importance of the compound for daily clinical practice.
Frontiers in Oncology, May 13, 2022
PubMed, Dec 4, 2009
Purpose: To investigate whether rutin retards selenite-induced cataractogenesis in Wistar rat pup... more Purpose: To investigate whether rutin retards selenite-induced cataractogenesis in Wistar rat pups. Methods: On postpartum day ten, Group I rat pups received an intraperitoneal injection of saline. Group II and III rat pups received a subcutaneous injection of sodium selenite. Group III also received an intraperitoneal injection of rutin once daily on postpartum days 9-14. Both eyes of each pup were examined from day 16 up to postpartum day 30. After sacrifice, extricated pup lenses were analyzed for mean activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase. In addition, the mean concentrations of reduced glutathione (GSH) and of malondialdehyde were analyzed in samples of lenses and hemolysate. Results: There was dense lenticular opacification in all of Group II, minimal opacification in 33.3% of Group III, no opacification in 66.7% of Group III, and no opacification in Group I. Significantly lower mean activities of lenticular antioxidant enzymes were noted in Group II, compared to Group I and III. Significantly lower mean concentrations of GSH and higher mean concentrations of malondialdehyde were noted in samples of hemolysate and lens from Group II, compared to the values in Group I and III. Conclusion: Rutin prevents experimental selenite-induced cataractogenesis in rat pups, possibly by preventing depletion of antioxidant enzymes and of GSH, and by inhibiting lipid peroxidation.
Molecular Cancer Research, May 9, 2022
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer, as it commonly... more Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer, as it commonly metastasizes to the liver resulting in an overall poor prognosis. However, the molecular mechanism involved in liver metastasis remains poorly understood. Here, we aimed to identify the MUC16-mediated molecular mechanism of PDAC-liver metastasis. Previous studies demonstrated that MUC16 and its C-terminal (Cter) domain are involved in the aggressiveness of PDAC. In the present study, we observed MUC16 and its Cter expression significantly high in human PDAC tissues, PDAC organoids, and metastatic liver tissues, while no expression was observed in normal pancreatic tissues using immunohistochemistry (IHC) and immunofluorescence (IFC) analyses. MUC16 knockdown in SW1990 and CD18/HPAF PDAC cells significantly decreased the colony formation, migration, and endothelial/p-selectin binding. In contrast, MUC16-Cter ectopic overexpression showed significantly increased colony formation and motility in MiaPaCa2 PC cells. Interestingly, MUC16 promoted cell survival and colonization in the liver, mimicking an ex vivo environment. Furthermore, MUC16 enhanced liver metastasis in the in vivo mouse model. Our integrated analyses of RNA-seq suggested that MUC16 alters Neuropilin-2 (NRP2) and cell adhesion molecules in PC cells. Furthermore, we identified that MUC16 regulated NRP2 via JAK2/STAT1 signaling in PDAC. NRP2 knockdown in MUC16 overexpressed PDAC cells showed significantly decreased cell adhesion and migration. Overall, the findings indicate that MUC16 regulates NRP2 and induces metastasis in PDAC.Implications:This study shows that MUC16 plays a critical role in PDAC liver metastasis by mediating NRP2 regulation by JAK2/STAT1 axis, thereby paving the way for future therapy efforts for metastatic PDAC.
Experimental Eye Research, Feb 1, 2008
Pancreas, Oct 13, 2020
Objectives Elevated neutrophil gelatinase–associated lipocalin (NGAL) is a promising marker for s... more Objectives Elevated neutrophil gelatinase–associated lipocalin (NGAL) is a promising marker for severe acute pancreatitis (SAP) and multiple organ failure, suggesting systemic and local contributions during pancreatitis. We investigated the role of NGAL locally on acinar cell biology. Methods Western blot, reverse transcriptase–polymerase chain reaction, and immunohistochemistry analysis were performed to analyze the levels of NGAL receptors, apoptotic and regeneration markers, and 4-hydroxynonenal (4HNE) levels, 3-[4,5-Dimethylthiazole-2-yl]-2, 5-diphenyltetrazolium bromide assay, and annexin V/propidium iodide staining were used to evaluate cell viability, and effect on endothelial cells was accessed by endothelial permeability assay. Results Cerulein treatment at 20 μM for 12 hours significantly reduced acinar cell viability by 40%, which was rescued by NGAL at 800 and 1600 ng/mL concentrations, observed during mild and SAP, respectively. Mechanistically, NGAL significantly reduced the levels of reactive oxygen species and 4HNE adduct formation in a 24p3R-dependent manner and upregulated the expression of acinar cell regeneration markers, like CDK-2, CDK-4, and C-myc. However, SAP levels of NGAL significantly increased endothelial permeability and downregulated the levels of ZO-1, and cerulein treatment in NGAL knockout mice showed increased levels of 4HNE adducts. Conclusions Neutrophil gelatinase–associated lipocalin rescues intracellular reactive oxygen species during pancreatitis and promotes survival and regeneration of acinar cells.
The Scientific World Journal, 2015
Cancer Research
Background: Docetaxel has been the most effective chemotherapeutic option after the emergence of ... more Background: Docetaxel has been the most effective chemotherapeutic option after the emergence of Castration-resistant prostate cancer (CRPC). However, more than 50% of patients develop Docetaxel Resistance (DoceR) within three years of treatment. It also shows severe adverse effects that lead to dose reduction and treatment failure. Thus, targeting the underlying mechanism of DoceR could improve survival benefits for CRPC patients. In this study, we identified leukemia inhibitory factor receptor (LIFR) as a candidate for DoceR. We targeted it with EC914, a first-in-class oral small molecule, to overcome DoceR in CRPC. Methods: We developed three DoceR (PC3-R60, 22Rv1-R110, and LNCaP(C-83)-R50) isogeneic sub-lines by chronic Docetaxel treatment for six months. We analyzed those cell lines for drug resistance markers using RT-PCR and western blot. We evaluated the effect of EC914 in overcoming DoceR using cytotoxicity assay in Incucyte® live imaging system, colony survival assay, apop...
Supplementary Table from MUC16 Promotes Liver Metastasis of Pancreatic Ductal Adenocarcinoma by U... more Supplementary Table from MUC16 Promotes Liver Metastasis of Pancreatic Ductal Adenocarcinoma by Upregulating NRP2-Associated Cell Adhesion
Supplementary Figure from MUC16 Promotes Liver Metastasis of Pancreatic Ductal Adenocarcinoma by ... more Supplementary Figure from MUC16 Promotes Liver Metastasis of Pancreatic Ductal Adenocarcinoma by Upregulating NRP2-Associated Cell Adhesion
Oncogene
MUC16, membrane-bound mucin, plays an oncogenic role in pancreatic ductal adenocarcinoma (PDAC). ... more MUC16, membrane-bound mucin, plays an oncogenic role in pancreatic ductal adenocarcinoma (PDAC). However, the pathological role of MUC16 in the PDAC progression, tumor microenvironment, and metastasis in cooperation with Kras G12D and Trp53 R172H mutations
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Nanomedicine: Nanotechnology, Biology and Medicine
www.impactjournals.com/oncotarget / Oncotarget, Vol. 6, No.6
JNCI: Journal of the National Cancer Institute, 2018
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with high morbidit... more Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with high morbidity and mortality. Racial disparity in HNSCC is observed between African Americans (AAs) and whites, effecting both overall and 5-year survival, with worse prognosis for AAs. In addition to socioeconomic status and demographic factors, many epidemiological studies have also identified factors including coexisting human papillomavirus (HPV) infection, primary tumor location, and a variety of somatic mutations that contribute to the prognostic incongruities in HNSCC patients among AAs and whites. Recent research also suggests HPV-induced dysregulation of tumor metabolism and immune microenvironment as the major regulators of HNSCC patient prognosis. Outcomes of several preclinical and clinical studies on targeted therapeutics warrant the need to elucidate the inherent mechanistic and population-based disparities underlying patient responses. This review systematically reports the underlying reasons for inconsistency in disease prognosis and therapy responses among HNSCC patients from different racial populations. The focus of this review is twofold: aside from discussing the causes of racial disparity, we also seek to identify the consequences of such disparity in terms of HPV infection and its associated mutational, metabolic, and immune landscapes. Considering the clinical impact of differential patient outcomes among AA and white populations, understanding the underlying cause of this disparity may pave the way for novel precision therapy for HNSCC. REVIEW
Molecular vision, Jan 31, 2009
To investigate whether acetyl-L-carnitine (ALCAR) retards L-buthionine-(S,R)-sulfoximine (BSO)-in... more To investigate whether acetyl-L-carnitine (ALCAR) retards L-buthionine-(S,R)-sulfoximine (BSO)-induced cataractogenesis in Wistar rat pups. On postpartum day 3, group I pups received intraperitoneal (ip) saline and group II and group III pups received i.p. injections of BSO once daily for three consecutive days. In addition, group III pups received ip ALCAR once daily from postpartum days 3-15. Both eyes of each pup were examined up from postpartum day 16 to day 30. After sacrifice, extricated pup lenses were analyzed for antioxidant and redox system components. There was dense lenticular opacification in all group II pups, minimal opacification in 40% of group III pups, and no opacification in 60% of group III pups and in all of group I pups. Group II lenses exhibited significantly lower values of antioxidant and redox system components and higher malondialdehyde concentrations than in group I or group III lenses. ALCAR prevents cataractogenesis in the BSO-induced cataract model, p...
Experimental Eye Research, 2009
The present study sought to determine whether acetyl-L-carnitine (ALCAR) prevents selenite catara... more The present study sought to determine whether acetyl-L-carnitine (ALCAR) prevents selenite cataractogenesis by mechanisms involving lenticular calpain activity, Wistar rat pups were divided into 3 groups of 15 each. Group I (normal) rats received an intraperitoneal (i.p.) injection of normal saline on postpartum day 10; Group II (cataract-untreated) rats received a single subcutaneous (s.c.) injection of sodium selenite (19micromol/kg body weight) on postpartum day 10; Group III (cataract-treated) pups received a single s.c. injection of sodium selenite on postpartum day 10 and intraperitoneal injections of acetyl-L-carnitine (200mg/kg body weight) on postpartum days 9-14. At the end of the study period (postpartum day 16), both eyes of each rat pup were examined by slit-lamp biomicroscopy. There was dense lenticular opacification in all Group II rats, minimal lenticular opacification in 33% of Group III rats, and no lenticular opacification in 67% of Group III and in all Group I rats. Group II lenses exhibited significantly lower mean values of calpain activity and Lp82 (lens-specific calpain) protein expression, decreases in relative transcript level of m-calpain mRNA and significantly higher mean Ca(2+) concentrations than Group I or Group III lenses; the values of these parameters in Group III rat lenses (ALCAR-treated) approximated those in Group I rat lenses. The results suggest that, in addition to its already-described antioxidant potential, ALCAR prevents selenite cataractogenesis by maintaining calpain activity at near normal levels. These findings may stimulate further efforts to develop ALCAR as a novel drug for prevention of cataract.
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Papers by Sakthivel Muniyan