'Ouabain, a potent inhibitor of the Na+/K+-ATPase pump, selectively destroys spiral ganglion neurons (SGNs) in gerbils and mice, whereas in guinea pigs it preferentially damages cochlear hair cells. To elucidate the effects of ouabain on the rat inner ear, a species widely used in research, 5 µl of 1 or ... More
An anti-transferrin receptor-avidin fusion protein exhibits both strong proapoptotic activity and the ability to deliver various molecules into cancer cells.
AuthorsNg PP, Dela Cruz JS, Sorour DN, Stinebaugh JM, Shin SU, Shin DS, Morrison SL, Penichet ML
JournalProc Natl Acad Sci U S A
PubMed ID12149472
'We have developed an antibody fusion protein (anti-rat TfR IgG3-Av) with the ability to deliver different molecules into cancer cells. It consists of avidin genetically fused to the C(H)3 region of a human IgG3 specific for the rat transferrin receptor. It forms strong, noncovalent interactions with biotinylated molecules such as ... More
Inositol pyrophosphate synthesis by inositol hexakisphosphate kinase 1 is required for homologous recombination repair.
'Inositol pyrophosphates, such as diphosphoinositol pentakisphosphate (IP(7)), are water-soluble inositol phosphates that contain high energy diphosphate moieties on the inositol ring. Inositol hexakisphosphate kinase 1 (IP6K1) participates in inositol pyrophosphate synthesis, converting inositol hexakisphosphate (IP(6)) to IP(7). In the present study, we show that mouse embryonic fibroblasts (MEFs) lacking IP6K1 ... More
Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia models.
AuthorsPortwood S, Lal D, Hsu YC, Vargas R, Johnson MK, Wetzler M, Hart CP, Wang ES,
Journal
PubMed ID24088735
'Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm. Recent evidence has shown the bone marrow microenvironment in patients with AML to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to survive under low oxygenation also confer chemoresistance. We therefore asked whether therapeutic exploitation of marrow hypoxia via the ... More
Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion.
AuthorsRalston KS, Solga MD, Mackey-Lawrence NM, Somlata, Bhattacharya A, Petri WA,
Journal
PubMed ID24717428
'Entamoeba histolytica is the causative agent of amoebiasis, a potentially fatal diarrhoeal disease in the developing world. The parasite was named '
Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures.
AuthorsQi W, Ding D, Salvi RJ,
JournalHear Res
PubMed ID18207679
'The amphipathic molecule dimethyl sulphoxide (DMSO) is a solvent often used to dissolve compounds applied to the inner ear; however, little is known about its potential cytotoxic side effects. To address this question, we applied 0.1-6% DMSO for 24h to cochlear organotypic cultures from postnatal day 3 rats and examined ... More
Detection of apoptotic cells in whole saliva of patients with oral premalignant and malignant lesions: a preliminary study.
AuthorsCheng B, Rhodus NL, Williams B, Griffin RJ
JournalOral Surg Oral Med Oral Pathol Oral Radiol Endod
PubMed ID15088030
'OBJECTIVE: The purpose of this study was to identify and measure apoptotic cells in whole saliva of patients with oral premalignant and malignant lesions and explore its utility as a prognostic indicator. STUDY DESIGN: A fluorescent TUNEL technique (APO-BrdU TUNEL) modified by our lab was applied to unstimulated whole saliva ... More
Up-regulation of the neuronal nicotinic receptor a7 by HIV glycoprotein 120: potential implications for HIV-associated neurocognitive disorder.
AuthorsBallester LY, Capó-Vélez CM, García-Beltrán WF, Ramos FM, Vázquez-Rosa E, Ríos R, Mercado JR, Meléndez RI, Lasalde-Dominicci JA,
JournalJ Biol Chem
PubMed ID22084248
'Approximately 30-50% of the >30 million HIV-infected subjects develop neurological complications ranging from mild symptoms to dementia. HIV does not infect neurons, and the molecular mechanisms behind HIV-associated neurocognitive decline are not understood. There are several hypotheses to explain the development of dementia in HIV(+) individuals, including neuroinflammation mediated by ... More
Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice.
AuthorsMeira LB, Moroski-Erkul CA, Green SL, Calvo JA, Bronson RT, Shah D, Samson LD,
JournalProc Natl Acad Sci U S A
PubMed ID19139400
Vision loss affects >3 million Americans and many more people worldwide. Although predisposing genes have been identified their link to known environmental factors is unclear. In wild-type animals DNA alkylating agents induce photoreceptor apoptosis and severe retinal degeneration. Alkylation-induced retinal degeneration is totally suppressed in the absence of the DNA ... More
Cytochemical methods for the detection of apoptosis.
AuthorsWillingham MC
JournalJ Histochem Cytochem
PubMed ID10449530
Detection of apoptotic cell death in cells and tissues has become of paramount importance in many fields of modern biology, including studies of embryonic development, degenerative disease, and cancer biology. In addition to methods that employ biochemical analysis of large populations of cells, cytochemical methods have recently been extensively used ... More
Unexpected gain of function for the scaffolding protein plectin due to mislocalization in pancreatic cancer.
AuthorsShin SJ, Smith JA, Rezniczek GA, Pan S, Chen R, Brentnall TA, Wiche G, Kelly KA,
Journal
PubMed ID24218614
We recently demonstrated that plectin is a robust biomarker for pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive malignancies. In normal physiology, plectin is an intracellular scaffolding protein, but we have demonstrated localization on the extracellular surface of PDAC cells. In this study, we confirmed cell surface localization. Interestingly, ... More
Outflow tract ablation using a conditionally cytotoxic feline immunodeficiency viral vector.
To create an in vivo model of vector-mediated trabecular meshwork (TM) ablation and replacement. We generated a conditionally cytotoxic, trackable vector, HSVtkiG, that expressed herpes simplex virus 1 thymidine kinase (HSVtk) and enhanced green fluorescent protein (eGFP). We optimized HSVtkiG ablation in vitro with ganciclovir (GCV) in comparison to eGFP ... More
Bortezomib and SAHA synergistically induce ROS-driven caspase-dependent apoptosis of nasopharyngeal carcinoma and block replication of Epstein-Barr virus.
AuthorsHui KF, Lam BH, Ho DN, Tsao SW, Chiang AK,
JournalMol Cancer Ther
PubMed ID23475956
A novel drug combination of a proteasome inhibitor, bortezomib, and a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), was tested in nasopharyngeal carcinoma (NPC), both in vitro and in vivo. Dose-response of different concentrations of bortezomib and SAHA on inhibition of cell proliferation of NPC was determined. Mechanisms of apoptosis ... More
Activation of a PGC-1-related coactivator (PRC)-dependent inflammatory stress program linked to apoptosis and premature senescence.
AuthorsGleyzer N, Scarpulla RC,
JournalJ Biol Chem
PubMed ID23364789
PGC-1-related coactivator (PRC), a growth-regulated member of the PGC-1 coactivator family, contributes to the expression of the mitochondrial respiratory apparatus. PRC also orchestrates a robust response to metabolic stress by promoting the expression of multiple genes specifying inflammation, proliferation, and metabolic reprogramming. Here, we demonstrate that this PRC-dependent stress program ... More
Timeless-dependent DNA replication-coupled recombination promotes Kaposi's Sarcoma-associated herpesvirus episome maintenance and terminal repeat stability.
AuthorsDheekollu J, Chen HS, Kaye KM, Lieberman PM,
JournalJ Virol
PubMed ID23325691
Kaposi's Sarcoma-associated herpesvirus (KSHV) is maintained as a stable episome in latently infected pleural effusion lymphoma (PEL) cells. Episome maintenance is conferred by the binding of the KSHV-encoded LANA protein to the viral terminal repeats (TR). Here, we show that DNA replication in the KSHV TR is coupled with DNA ... More
Directional release of reovirus from the apical surface of polarized endothelial cells.
AuthorsLai CM, Mainou BA, Kim KS, Dermody TS,
JournalMBio
PubMed ID23572551
Bloodstream spread is a critical step in the pathogenesis of many viruses. However, mechanisms that promote viremia are not well understood. Reoviruses are neurotropic viruses that disseminate hematogenously to the central nervous system. Junctional adhesion molecule A (JAM-A) is a tight junction protein that serves as a receptor for reovirus. ... More
Doxorubicin blocks proliferation of cancer cells through proteolytic activation of CREB3L1.
AuthorsDenard B, Lee C, Ye J,
JournalElife
PubMed ID23256041
Doxorubicin is used extensively for chemotherapy of diverse types of cancer, yet the mechanism through which it inhibits proliferation of cancer cells remains unclear. Here we report that doxorubicin stimulates de novo synthesis of ceramide, which in turn activates CREB3L1, a transcription factor synthesized as a membrane-bound precursor. Doxorubicin stimulates ... More
The opposite roles of glucocorticoid and a1-adrenergic receptors in stress triggered apoptosis of rat Leydig cells.
AuthorsAndric SA, Kojic Z, Bjelic MM, Mihajlovic AI, Baburski AZ, Sokanovic SJ, Janjic MM, Stojkov NJ, Stojilkovic SS, Kostic TS,
JournalAm J Physiol Endocrinol Metab
PubMed ID23149620
The stress-induced initiation of proapoptotic signaling in Leydig cells is relatively well defined, but the duration of this signaling and the mechanism(s) involved in opposing the stress responses have not been addressed. In this study, immobilization stress (IMO) was applied for 2 h daily, and animals were euthanized immediately after ... More
Electron transfer-based combination therapy of cisplatin with tetramethyl-p-phenylenediamine for ovarian, cervical, and lung cancers.
AuthorsLuo T, Yu J, Nguyen J, Wang CR, Bristow RG, Jaffray DA, Zhou XZ, Lu KP, Lu QB,
JournalProc Natl Acad Sci U S A
PubMed ID22685209
The platinum-based chemotherapy is the standard treatment for several types of cancer. However, cancer cells often become refractory with time and most patients with serious cancers die of drug resistance. Recently, we have discovered a unique dissociative electron-transfer mechanism of action of cisplatin, the first and most widely used platinum-based ... More
Downregulation of the CCK-B receptor in pancreatic cancer cells blocks proliferation and promotes apoptosis.
AuthorsFino KK, Matters GL, McGovern CO, Gilius EL, Smith JP,
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID22442157
Gastrin stimulates the growth of pancreatic cancer cells through the activation of the cholecystokinin-B receptor (CCK-BR), which has been found to be overexpressed in pancreatic cancer. In this study, we proposed that the CCK-BR drives growth of pancreatic cancer; hence, interruption of CCK-BR activity could potentially be an ideal target ... More
Cardiac morphogenesis: matrix metalloproteinase coordination of cellular mechanisms underlying heart tube formation and directionality of looping.
AuthorsLinask KK, Han M, Cai DH, Brauer PR, Maisastry SM,
JournalDev Dyn
PubMed ID15844197
During heart organogenesis, the spatiotemporal organization of the extracellular matrix (ECM) undergoes significant remodeling. Because matrix metalloproteinases (MMPs) are known to be key regulators of cell-matrix interactions, we analyzed the role(s) of MMPs, and specifically MMP-2, in early heart development. Both MMP-2 neutralizing antibody and the broad-spectrum MMP inhibitor Ilomastat ... More
Cross-regulation between oncogenic BRAF(V600E) kinase and the MST1 pathway in papillary thyroid carcinoma.
AuthorsLee SJ, Lee MH, Kim DW, Lee S, Huang S, Ryu MJ, Kim YK, Kim SJ, Kim SJ, Hwang JH, Oh S, Cho H, Kim JM, Lim DS, Jo YS, Shong M,
JournalPLoS One
PubMed ID21249150
The BRAF(V600E) mutation leading to constitutive signaling of MEK-ERK pathways causes papillary thyroid cancer (PTC). Ras association domain family 1A (RASSF1A), which is an important regulator of MST1 tumor suppressor pathways, is inactivated by hypermethylation of its promoter region in 20 to 32% of PTC. However, in PTC without RASSF1A ... More
Analysis of apoptosis by cytometry using TUNEL assay.
AuthorsDarzynkiewicz Z, Galkowski D, Zhao H,
JournalMethods
PubMed ID18314056
Activation of endonucleases that cleave chromosomal DNA preferentially at internucleosomal sections is a hallmark of apoptosis. DNA fragmentation revealed by the presence of a multitude of DNA strand breaks, therefore, is considered to be the gold standard for identification apoptotic cells. Several variants of the methodology that is based on ... More
In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models.
The pathways underlying basal-like breast cancer are poorly understood, and as yet, there is no approved targeted therapy for this disease. We investigated the role of mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) inhibitors as targeted therapies for basal-like breast cancer. We used pharmacogenomic analysis of a large ... More
Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart.
AuthorsOtt HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, Taylor DA,
JournalNat Med
PubMed ID18193059
About 3,000 individuals in the United States are awaiting a donor heart; worldwide, 22 million individuals are living with heart failure. A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Generating a bioartificial heart requires engineering of cardiac architecture, appropriate cellular constituents and pump function. ... More
In vitro catabolic effect of protoporphyrin IX in human osteoblast-like cells: possible role of the 18 kDa mitochondrial translocator protein.
AuthorsRosenberg N, Rosenberg O, Weizman A, Veenman L, Gavish M
JournalJ Bioenerg Biomembr
PubMed ID23475134
In several pathological conditions, when conversion of Protoporphyrin (PP)IX into heme is impaired, a toxic accumulation of PPIX might occur. PPIX has been found to have affinity to the mitochondrial Translocator Protein 18 kDa. Since it is known that TSPO is abundant in human osteoblast cells, thus we assumed that ... More
D-saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via NF-?B and PKC signaling.
AuthorsBhattacharya S, Manna P, Gachhui R, Sil PC
JournalToxicol Appl Pharmacol
PubMed ID23261973
Increasing evidence suggests that oxidative stress is involved in the pathogenesis of diabetic nephropathy (DN) and this can be attenuated by antioxidants. D-Saccharic acid 1,4-lactone (DSL) is known for its detoxifying and antioxidant properties. Our early investigation showed that DSL can ameliorate alloxan (ALX) induced diabetes mellitus and oxidative stress ... More
A 43 kD protein from the leaves of the herb Cajanus indicus L. modulates doxorubicin induced nephrotoxicity via MAPKs and both mitochondria dependent and independent pathways.
AuthorsPal S, Sil PC
JournalBiochimie
PubMed ID22429871
Doxorubicin (Dox), a chemotherapeutic drug, is used for the treatment of different types of cancers. Application of this drug has now been made limited because of its several acute and chronic side effects. The aim of this work is to investigate the nephroprotecive role of a 43 kD protein (CI protein) ... More
The prophylactic role of D-saccharic acid-1,4-lactone against hyperglycemia-induced hepatic apoptosis via inhibition of both extrinsic and intrinsic pathways in diabetic rats.
AuthorsBhattacharya S, Gachhui R, Sil PC
JournalFood Funct
PubMed ID23138840
Sustained hyperglycemia and increased oxidative stress play major roles in the development of secondary complications in diabetes including liver injury. Dietary supplement of antioxidants is effective in preventing oxidative stress mediated tissue damage in diabetic pathophysiology. D-Saccharic acid 1,4-lactone (DSL), a derivative of D-glucaric acid, is present in many dietary ... More
IL-1 Receptor Antagonist Reduced Chemical-Induced Keratinocyte Apoptosis through Antagonism to IL-1a/IL-1ß.
AuthorsLee H, Cheong KA, Kim JY, Kim NH, Noh M, Lee AY
JournalBiomol Ther (Seoul)
PubMed ID29310426
'Extracellular interleukin 1 alpha (IL-1a) released from keratinocytes is one of the endpoints for'
Microenvironment-regulated lncRNA-HAL is able to promote stemness in breast cancer cells.
AuthorsGarcía-Venzor A, Mandujano-Tinoco EA, Lizarraga F, Zampedri C, Krötzsch E, Salgado RM, Dávila-Borja VM, Encarnación-Guevara S, Melendez-Zajgla J, Maldonado V
JournalBiochim Biophys Acta Mol Cell Res
PubMed ID31401107
'Multicellular Tumor Spheroids culture (MCTS) is an in vitro model mimicking the characteristics of the tumor microenvironment, such as hypoxia and acidosis, resulting in the presence of both proliferating and quiescent cell populations. lncRNA''s is a novel group of regulatory molecules that participates in the acquisition of tumorigenic phenotypes. In ... More
Role of MAPK/NF-?B pathway in cardioprotective effect of Morin in isoproterenol induced myocardial injury in rats.
AuthorsVerma VK, Malik S, Narayanan SP, Mutneja E, Sahu AK, Bhatia J, Arya DS
JournalMol Biol Rep
PubMed ID30666500
'Oxidative stress plays a major role in myocardial injury. Morin, a bioflavonoid has known to possess various biological activities in previous studies. Hence, this study evaluated the cardioprotective mechanism(s) of Morin against isoproterenol induced myocardial necrosis in rats. Male albino Wistar rats were divided into five groups (n?=?8) i.e., I ... More
Obesity-associated family with sequence similarity 13, member A (FAM13A) is dispensable for adipose development and insulin sensitivity.
AuthorsTang J, Zhou H, Sahay K, Xu W, Yang J, Zhang W, Chen W
JournalInt J Obes (Lond)
PubMed ID30301961
'Obesity and its associated morbidities represent the major and most rapidly expanding world-wide health epidemic. Recent genome-wide association studies (GWAS) reveal that single nucleotide polymorphism (SNP) variant in the Family with Sequence Similarity 13, Member A (FAM13A) gene is strongly associated with waist-hip ratio (WHR) with adjustment for body mass ... More
Amphotericin B potentiates the anticancer activity of doxorubicin on the MCF-7 breast cancer cells.
AuthorsTavangar F, Sepehri H, Saghaeian Jazi M, Asadi J
JournalJ Chem Biol
PubMed ID28685000
Despite the improvements in cancer treatment, breast cancer still remains the second most common cause of death from cancer in women. Doxorubicin (DOXO) is widely used for cancer treatment. However, drug resistance limits the treatment outcome. Here, we investigated the toxicity of DOXO in combination with an antifungal agent amphotericin ... More
AuthorsAllende ML, Cook EK, Larman BC, Nugent A, Brady JM, Golebiowski D, Sena-Esteves M, Tifft CJ, Proia RL
JournalJ Lipid Res
PubMed ID29358305
Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of ß-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the ... More
MicroRNA-664 suppresses the growth of cervical cancer cells via targeting c-Kit.
AuthorsLv M, Ou R, Zhang Q, Lin F, Li X, Wang K, Xu Y
JournalDrug Des Devel Ther
PubMed ID31409971
Cervical cancer is the second most common malignant cancer in women worldwide. Evidence indicated that miR-664 was significantly downregulated in cervical cancer. However, the mechanisms by which miR-664 regulates the tumorigenesis of cervical cancer remain unclear. Thus, this study aimed to investigate the role of miR-664 in cervical cancer. ... More