Thermoactivatable polymer-grafted liposomes for low-invasive image-guided chemotherapy.

The objective of this study was to develop a thermotriggered, polymer-based liposomal drug carrier with an activatable magnetic resonance imaging (MRI) contrast property for monitoring the release of substances and for localized tumor therapy. The multimodal thermoactivatable polymer-grafted liposomes (MTPLs) were tested to investigate whether the accumulation of MTPLs in colon-26 grafted tumors could be visualized in vivo using MRI and optical imaging, whether MTPLs induce signal enhancement, reflecting the release of their contents, after triggering by short-term heating (42.5°C for 10 minutes) 9 hours after MTPL administration (late-phase triggering), and whether MTPLs can provide a sufficient antitumor effect.

Evaluation of selective tumor detection by clinical magnetic resonance imaging using antibody-conjugated superparamagnetic iron oxide.

Active targeting by monoclonal antibodies (mAbs) combined with nanosize superparamagnetic iron oxide (SPIO) is a promising technology for magnetic resonance imaging (MRI) diagnosis. However, the clinical applicability of this technology has not been investigated using appropriate controls. It is important to evaluate the targeting technology using widely used clinical 1.

Identification of SNF2h, a chromatin-remodeling factor, as a novel binding protein of Vpr of human immunodeficiency virus type 1.

Vpr, an accessory gene of human immunodeficiency virus type 1, encodes a virion-associated nuclear protein that plays an important role in the primary viral infection of resting macrophages. It has a variety of biological functions, including roles in a cell cycle abnormality at G(2)/M phase, apoptosis, nuclear transfer of preintegration complex, and DNA double-strand breaks (DSBs), some of which depend on its association with the chromatin of the host cells. Given that DSB signals are postulated to be a positive factor in the viral infection, understanding the mode of chromatin recruitment of Vpr is important.

Induction of long interspersed nucleotide element-1 (L1) retrotransposition by 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct.

Long interspersed nucleotide element-1 (L1) is a retroelement comprising about 17% of the human genome, of which 80-100 copies are competent as mobile elements (retrotransposition: L1-RTP). Although the genetic structures modified during L1-RTP have been clarified, little is known about the cellular signaling cascades involved. Herein we found that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct postulated as a candidate physiological ligand of the aryl hydrocarbon receptor (AhR), induces L1-RTP.

Vpr-induced DNA double-strand breaks: molecular mechanism and biological relevance.

We focus on the role of Vpr in inducing DNA double-strand breaks (DSBs) in the host cell. Based on the summarized findings of Vpr-induced DSBs and the finding of Vpr in the plasma of HIV-1-positive patients, we discuss the roles of Vpr in viral infection, especially viral infection of resting macrophages. We also describe the possible involvement of Vpr in non-AIDS-defining cancers, which represent an emerging crisis in HIV-1-positive patients.

IKK antagonizes CD95 ligation-mediated apoptosis by regulating NF-kappaB activity.

The CD95 (Apo1/Fas)/CD95 ligand system plays pivotal roles in various aspects of immune regulation and function by triggering apoptosis. Besides the apoptosis signaling pathway, CD95 ligation also induces the activation of NF-kappaB. Previous studies suggest that IkappaB kinase (IKK) may be a key player in cell survival by mediating NF-kappaB activation.

NF-kappaB is required for UV-induced JNK activation via induction of PKCdelta.

Ultraviolet (UV) exerts its biological activities by activating downstream effectors, including NF-kappaB, JNK, and caspases. Activation of JNK is required for UV-induced apoptosis. It is unknown whether any crosstalk occurs between NF-kappaB and JNK in response to UV and, if so, how it affects UV killing.

c-Jun N-terminal protein kinase 1 (JNK1), but not JNK2, is essential for tumor necrosis factor alpha-induced c-Jun kinase activation and apoptosis.

Two ubiquitously expressed isoforms of c-Jun N-terminal protein kinase (JNK), JNK1 and JNK2, have shared functions and different functions. However, the molecular mechanism is unknown. Here we report that JNK1, but not JNK2, is essential for tumor necrosis factor alpha (TNF-alpha)-induced c-Jun kinase activation, c-Jun expression, and apoptosis.

JNK suppresses apoptosis via phosphorylation of the proapoptotic Bcl-2 family protein BAD.

JNK has been suggested to be proapoptotic, antiapoptotic, or have no role in apoptosis depending on the cell type and stimulus used. The precise mechanism of JNK action, under conditions when it promotes cell survival, is not entirely clear. Here, we report that JNK is required for IL-3-mediated cell survival through phosphorylation and inactivation of the proapoptotic Bcl-2 family protein BAD.

Pro-apoptotic ASY/Nogo-B protein associates with ASYIP.

We have previously shown that ectopic expression of the ASY/Nogo-B gene induced apoptosis in various cancer cell lines. Nogo-A, a splice variant of the ASY, has been reported to have an inhibitory effect on neuronal regeneration in the central nervous system. To investigate the mechanism of ASY-induced apoptosis or inhibition of neuronal regeneration, we cloned a cDNA for the ASY-interacting protein from the human cDNA library using the yeast two-hybrid method, and obtained a cDNA we designated as ASYIP.

Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation.

Most cell lines that lack functional p53 protein are arrested in the G2 phase of the cell cycle due to DNA damage. When the G2 checkpoint is abrogated, these cells are forced into mitotic catastrophe. A549 lung adenocarcinoma cells, in which p53 was eliminated with the HPV16 E6 gene, exhibited efficient arrest in the G2 phase when treated with adriamycin.