G/C/T Personality Patterns and Counseling

Roth, H. J.

doi:10.1177/107621758600900326

Cited by 16 publications

(20 citation statements)

References 2 publications

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“…Recent advances in the field of antisense oligonucleotide therapy have been particularly suggestive of a DNA receptor͞ transport mechanism. Studies in which antisense oligonucleotides have been used to inhibit viral genes (24)(25)(26)(27)(28) or as therapeutic agents for the treatment of cancer (29,30) have demonstrated both the utility of antisense as drugs and the importance of DNA binding proteins that mediate internalization. Several potential cell surface DNA binding proteins have been identified (7,9,10,13,17,18), but a clear demonstration of function has been difficult, due to limitations of cell culture systems and the difficulty of distinguishing adherent from internalized DNA (15).…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of a cell membrane nucleic acid channel

Hanss

Leal-Pinto

Bruggeman

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

118

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We have identified a 45-kDa protein purified from rat renal brush border membrane that binds short single-stranded nucleic acid sequences. This activity was purified, reconstituted in proteoliposomes, and then fused with model planar lipid bilayers. In voltage-clamp experiments, the reconstituted 45-kDa protein functioned as a gated channel that allows the passage of nucleic acids. Channel activity was observed immediately after addition of oligonucleotide. Channel activity was not observed in the absence of purified protein or of oligonucleotide or when protein was heat-inactivated prior to forming proteoliposomes. In the presence of symmetrical buffered solution and oligonucleotide, current passed linearly over the range of holding potentials tested. Conductance was 10.4 ؎ 0.4 picosiemens (pS) and reversal potential was 0.2 ؎ 1.7 mV. There was no difference in channel conductance or reversal potential between phosphodiester and phosphorothioate oligonucleotides. Ionsubstitution experiments documented a shift in reversal potential only when a concentration gradient for oligonucleotide was established, indicating that movement of oligonucleotide alone was responsible for current. Movement of oligonucleotide across the bilayer was confirmed by using 32 P-labeled oligonucleotides. Channel open probability decreased significantly in the presence of heparan sulfate. These studies provide evidence for a cell surface channel that conducts nucleic acids.

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Section: Discussionmentioning

confidence: 99%

Identification and characterization of a cell membrane nucleic acid channel

Hanss

Leal-Pinto

Bruggeman

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

118

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“…For these reasons, we sought to determine whether antiviral approaches targeting the EBNA-1 protein could inhibit EBV-induced cell proliferation. Previous studies showed that antisense oligonucleotides directed to EBNA-1 partially inhibited EBNA-1 expression and also suppressed B cell proliferation (28,29). However, sufficient quantities of antisense oligonucleotides cannot be efficiently delivered to B cells and their relatively short half-life inside cells has hindered utilization of this antiviral approach.…”

Section: Discussionmentioning

confidence: 99%

Growth arrest of Epstein–Barr virus immortalized B lymphocytes by adenovirus-delivered ribozymes

Huang

Stupack

Mathias

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Epstein-Barr virus (EBV) infection is associated with several human diseases that involve unrestricted proliferation of B lymphocytes. EBV nuclear antigen 1 (EBNA-1) is expressed in all EBV-infected cells and plays an essential role in persistence of the EBV genome. EBNA-1 has also been reported to have oncogenic potential. As an approach for treating EBV infections, we examined the capacity of EBNA-1 ribozymes delivered by recombinant adenoviruses to suppress EBNA-1 expression and to block virus-induced B cell proliferation. In contrast to primary B cells, EBVtransformed B lymphoblastoid cell lines expressed ␣v integrins, the adenovirus internalization receptors, and were also susceptible to adenovirus-mediated gene delivery. Adenovirus delivery of a specific ribozyme (RZ1) to lymphoblastoid cell lines, suppressed EBNA-1 mRNA and protein expression, significantly reduced the number of EBV genomes, and nearly abolished cell proliferation in low serum. Adenovirus delivery of RZ1 also prevented EBV infection of an established EBVnegative B cell line. These studies demonstrate the potential use of adenovirus-encoded ribozymes to treat EBV-induced lymphoproliferative disorders.

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“…So far, few investigators have reported antiviral-based strategies to target EBV cancers cells. Two approaches have been used: (i) antisense oligonucleotides have been demonstrated to inhibit viral oncoprotein expression such as LMP1 or EBNA1, resulting in cell proliferation decrease and enhanced sensitivity to chemotherapeutic agents in vitro (Roth et al, 1994;Kenney et al, 1998;Morgan et al, 2000). (ii) A second approach used sodium butyrate (Chung et al, 2000) or IR (Westphal et al, 2000) in combination with Ganciclovir.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, antisense oligonucleotides against LMP1 or EBNA1 have been associated with inhibition of viral oncoprotein expression, induction of apoptosis, and sensitization of EBV-positive cells to cytotoxic agents (Roth et al, 1994;Kenney et al, 1998;Morgan et al, 2000). However, antisense delivery remains extremely difficult to achieve in clinical applications, underlying the need for alternative approaches.…”

Section: Introductionmentioning

confidence: 99%

Antiviral agent Cidofovir decreases Epstein–Barr virus (EBV) oncoproteins and enhances the radiosensitivity in EBV-related malignancies

Abdulkarim¹,

Sabri

Zélénika

et al. 2003

Oncogene

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The Epstein-Barr virus (EBV) is involved in the carcinogenesis of several human cancers such as nasopharyngeal carcinoma (NPC) and Burkitt lymphoma (BL). Given the consistent role of EBV in transformation and maintenance of malignant phenotype, antiviral strategies provide an attractive approach to target EBVexpressing cells. In that aim, we have tested the Cidofovir, which is an acyclic nucleoside phosphonate analog known to exert an antiproliferative activity in some human virusrelated tumors. Here, we show that Cidofovir induces a downregulation of the EBV oncoprotein LMP1 associated with a decrease of the antiapoptotic Bcl-2 and an increase of the proapoptotic Bax protein in Raji (BL) and C15 (NPC) cells. Using BL cell line BL2 B95-8 (BL2 infected with the B95.8 strain of EBV), we addressed the relation between EBV genome expression and modulation of viral oncoproteins by Cidofovir and/or ionizing radiation (IR). Cidofovir was able to significantly reduce LMP1 and EBNA2 mRNA and protein expression. This effect was associated with inhibition of proliferation, stimulation of apoptosis, and decrease of Bcl-2 expression in BL2 B95.8 cells. In addition, Cidofovir enhanced the radiationinduced apoptosis and the radiosensitivity through the proteolytic cleavage of death effectors caspase-9 and -3, which was specifically induced by combined treatment in EBV-positive cells compared to their negative counterparts. Furthermore, the combined treatment in nude mice led to a complete tumor remission without increasing toxicity in two human EBV-related cancer xenografts (Raji and C15). These results provide the basis for a novel anticancer strategy to enhance the therapeutic ratio of IR in EBV-related cancers.

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G/C/T Personality Patterns and Counseling

Cited by 16 publications

References 2 publications

Identification and characterization of a cell membrane nucleic acid channel

Identification and characterization of a cell membrane nucleic acid channel

Growth arrest of Epstein–Barr virus immortalized B lymphocytes by adenovirus-delivered ribozymes

Antiviral agent Cidofovir decreases Epstein–Barr virus (EBV) oncoproteins and enhances the radiosensitivity in EBV-related malignancies

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