Publications by authors named "Usha Kasid"

DEPDC1B (aliases BRCC3, XTP8, XTP1) is a DEP (Dishevelled, Egl-1, Pleckstrin) and Rho-GAP-like domains containing predominately membrane-associated protein. Earlier, we and others have reported that DEPDC1B is a downstream effector of Raf-1 and long noncoding RNA lncNB1, and an upstream positive effector of pERK. Consistently, DEPDC1B knockdown is associated with downregulation of ligand-stimulated pERK expression.

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Aberrant regulation of EGFR is common in non-small cell lung carcinomas (NSCLC), and tumor resistance to targeted therapies has been attributed to emergence of other co-occurring oncogenic events, parallel bypass receptor tyrosine kinase pathways including IGF1R, and TNFα-driven adaptive response via NF-κB. TNFAIP8, TNFα-inducible protein 8, is an NF-κB-activated prosurvival and oncogenic molecule. TNFAIP8 expression protects NF-κB-null cells from TNFα-induced cell death by inhibiting caspase-8 activity.

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Tumor necrosis factor-α-inducible protein 8 (TNFAIP8) is the first discovered oncogenic and an anti-apoptotic member of a conserved TNFAIP8 or TIPE family of proteins. TNFAIP8 mRNA is induced by NF-kB, and overexpression of TNFAIP8 has been correlated with poor prognosis in many cancers. Downregulation of TNFAIP8 expression has been associated with decreased pulmonary colonization of human tumor cells, and enhanced sensitivities of tumor xenografts to radiation and docetaxel.

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Endoplasmic reticulum (ER) stress leads to activation of the unfolded protein response (UPR) signaling cascade and induction of an apoptotic cell death, autophagy, oncogenesis, metastasis, and/or resistance to cancer therapies. Mechanisms underlying regulation of ER transmembrane proteins PERK, IRE1α, and ATF6α/β, and how the balance of these activities determines outcome of the activated UPR, remain largely unclear. Here, we report a novel molecule transmembrane protein 33 (TMEM33) and its actions in UPR signaling.

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TNFAIP8 is a NF-κB-inducible, oncogenic molecule. Previous "promoter array" studies have identified differential methylation and regulation of TNFAIP8 in prostate epithelial and cancer cell lines. Here we demonstrate that TNFAIP8 expression is induced by androgen in hormone-responsive LNCaP prostate cancer cells.

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Purpose: BLID is a BH3-like motif containing apoptotic member of the Bcl-2 family of proteins. This study was designed to investigate the mechanism of BLID-induced apoptosis and to assess the significance of BLID expression in breast cancer.

Experimental Design: The interaction between BLID and Bcl-X(L) was examined using in vitro transcription/translation, coimmunoprecipitation, and immunoflourescence assays.

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By virtue of their potential to selectively silence oncogenic molecules in cancer cells, antisense oligonucleotides (ASO) and small interfering RNAs (siRNAs) are powerful tools for development of tailored anti-cancer drugs. The clinical benefit of ASO/siRNA therapeutic is, however, hampered due to poor pharmacokinetics and biodistribution, and suboptimal suppression of the target in tumor tissues. Raf-1 protein serine/threonine kinase is a druggable signaling molecule in cancer therapy.

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Antisense oligonucleotides (ASO) against specific molecular targets (e.g., Bcl-2 and Raf-1) are important reagents in cancer biology and therapy.

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Raf-1 protein serine/threonine kinase plays an important role in ERK signal transduction pathway of cell survival and proliferation. Raf-induced transcriptional changes are dependent on phosphorylation/activation of ERK. However, regulation of phospho-ERK (p-ERK) via Raf transcriptome is as yet unknown.

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Raf-1 serine/threonine protein kinase plays an important role in cell growth, differentiation and cell survival. Recent reports using c-raf-1 gene-knockouts have observed MEK/ERK independent functions of Raf-1 in cell survival and protection from apoptosis. Raf-1 has also been shown to be involved in counteracting specific apoptotic pathways by restraining caspase activation, although the precise mechanism is unknown.

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Purpose: Raf proteins are key elements of growth-related cellular signaling pathways and are a component of cancer cell resistance to radiation therapy. Antisense oligonucleotides to c-raf-1 permit highly selective inhibition of the gene product and offer a strategy for sensitizing cancer cells to radiation therapy. In this dose escalation study, we evaluated the safety of combined liposomal formulation of raf antisense oligonucleotide (LErafAON) and radiation therapy in patients with advanced malignancies.

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Raf-1 protein serine-threonine kinase plays an important role in cell growth, proliferation, and cell survival. Previously, we and others have demonstrated that antisense raf oligonucleotide-mediated inhibition of Raf-1 expression leads to tumor growth arrest, radiosensitization and chemosensitization in vivo. Raf-1 inhibition is also associated with apoptotic cell death.

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SCC-S2/GG2-1/NDED (approved gene symbol TNFAIP8) is a transcription factor NF-kappaB-inducible, antiapoptotic, and oncogenic molecule. In this study, we examined the role of SCC-S2 in invasion and experimental metastasis. We demonstrate that expression of SCC-S2 cDNA in MDA-MB 435 human breast cancer cells is associated with enhanced invasion in vitro and increased frequency of pulmonary colonization of tumor cells in athymic mice.

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Raf-1, a protein serine-threonine kinase, plays a critical role in mitogen-activated protein kinase kinase (MKK/MEK)- mitogen-activated protein kinase (extracellular signal-regulated kinase) (MAPK/ERK) pathways. We show here that systemically delivered novel cationic cardiolipin liposomes (NeoPhectin-AT) containing a small interfering RNA (siRNA) against Raf-1 silence the expression of Raf-1 in tumor tissues and inhibit tumor growth in xenograft model of human prostate cancer. The knockdown of Raf-1 expression by siRNA is also associated with down-regulation of cyclin D1 expression in vivo.

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Despite significant evidence of a role of hypoxia in cellular resistance to ionizing radiation-induced toxicity, the underlying molecular mechanisms remain unclear. This study focused on the influence of hypoxia on radiation-induced signals in TK6 human lymphoblastoid cells. Hypoxic (<10 ppm oxygen) and aerobic cells were exposed to equilethal doses of ionizing radiation, radiation dose ratio, 3:1 (hypoxia:air).

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Background: In previous studies, nitroxide tempo (2, 2, 6, 6-tetramethyl-piperidine-1-oxyl), a small molecule, induced cell death in cancer cells. The current study examined the antineoplastic properties of tempo in the human hormone-dependent/hormone-independent prostate carcinoma models (LNCaP, DU-145, and PC-3).

Methods: The apoptotic effects of tempo were examined by the flow cytometric analysis of cells labeled with fluorescein isothiocyanate-conjugated annexin-V, and by electron microscopy.

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Purpose: Rapid cleavage in vivo and inefficient cellular uptake limit the clinical utility of antisense oligonucleotides (AON). Liposomal formulation may promote better intratumoral AON delivery and inhibit degradation in vivo. We conducted the first clinical evaluation of this concept using a liposomal AON complementary to the c-raf-1 proto-oncogene (LErafAON).

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We report here the structure-functional characterization of a novel intronless gene, BRCC2, located on human chromosome 11q24.1. BRCC2 open reading frame (327 bp) codes for an approximately 12-kDa protein (108 amino acids (aa)) localized predominantly in the cytosol and to a lesser extent in the mitochondria.

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Raf-1 protein kinase plays an important role in cell growth, proliferation and cell survival. We have previously described the use of liposome-entrapped antisense raf oligonucleotide (LErafAON) to inhibit Raf-1 expression resulting in tumor growth inhibition and radiosensitization. The present study was undertaken to evaluate the chemosensitization effects of LErafAON in combination with doxorubicin or paclitaxel on a panel of human tumor xenografts.

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We report here the identification and an initial characterization of a novel cell cycle-regulated molecule, SCC-112. SCC-112 cDNA (6744 bp) encodes a longest open reading frame (ORF) comprised of 1297 amino acids, representing a approximately 150-kDa nuclear protein. SCC-112 mRNA and protein levels were relatively high during the G2/M phase of the cell cycle in MDA-MB 435 breast cancer cells.

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Raf-1 protein serine/threonine kinase plays an important role in cell proliferation and cell survival. We have previously described a novel cationic liposome-entrapped formulation of raf antisense oligodeoxyribonucleotide (LErafAON) and its use as a radiosensitizer. The aim of this study was to examine the effect of combination of LErafAON and a chemotherapeutic agent on growth of human prostate (PC-3) and pancreatic tumor xenografts in athymic mice (Aspc-1 and Colo 357).

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SCC-S2/GG2-1/NDED is a recently discovered antiapoptotic molecule induced by the activation of the transcription factor NF-kappaB. Here we have examined a role of SCC-S2 in cell growth regulation in vitro and in vivo. Western blotting using an antipeptide antibody revealed endogenous SCC-S2 as a approximately 21 kDa cytosolic protein in human breast cancer cells (MDA-MB 231) and renal carcinoma cells (RCC-RS).

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The RAF-1 serine-threonine kinase plays a central role in signal transduction pathways involved in cell survival and proliferation. The concept of RAF-1-targeted disruption of cell signaling for therapeutic purposes was first advanced in 1989 with the demonstration of tumor growth inhibition in athymic mice and radiosensitization of human squamous carcinoma cells transfected with a vector expressing antisense cDNA. However, the clinical application of antisense strategies has awaited the development of improved antisense oligonucleotide technologies and drug delivery methods.

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Raf-1 protein serine threonine kinase plays an important role in cell survival and proliferation. Antisense inhibition of Raf-1 expression has been shown to enhance the cytotoxic effects of radiation and anticancer drugs. Here we have evaluated the toxicity, pharmacokinetics, and antitumor efficacy of a novel formulation of liposome-entrapped raf antisense oligodeoxyribonucleotide (LErafAON).

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Raf-1 serine/threonine protein kinase plays an important role in cell survival, proliferation, and migration; however, the specific targets of Raf-1 in diverse cellular processes are not clearly defined. Myosin phosphatase activity is critical to the regulation of cytoskeletal reorganization, cytokinesis, and cell motility. Here, we describe the association of Raf-1 with myosin phosphatase and phosphorylation of the regulatory myosin-binding subunit (MBS) of myosin phosphatase by Raf-1.

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