Tumor-stromal opening via S. typhimurium VNP20009 administration for complete inhibition of refractory tumor growth with liposomal anticancer drugs.

Many clinical tumors exhibit a vascular endothelium covered by mural cells and stroma with abundant collagen fibers, which greatly inhibit the penetration of nanoparticle drug delivery systems (DDS) formulations deep into the tumors. We previously found that Salmonella typhimurium VNP20009 attracting attention as live bacterial therapeutics, which is a novel pharmaceutical modality for cancer treatment, can grow within deep tumors with abundant stroma and tight vasculature. Because this finding interestingly indicates that VNP20009 administration disrupts vascular and stromal structures even in refractory tumors, we investigated the possibility that VNP20009 administration improves DDS formulations migrations into tumors in this study.

Robotic cell processing facility for clinical research of retinal cell therapy.

The consistent production of high-quality cells in cell therapy highlights the potential of automated manufacturing. Humanoid robots are a useful option for transferring technology to automate human cell cultures. This study evaluated a robotic cell-processing facility (R-CPF) for clinical research on retinal cell therapy, incorporating the versatile humanoid robot Maholo LabDroid and an All-in-One CP unit.

JCM1395 Achieved Intratumoral Growth with Minimal Inflammation: Evidence for Live Bacterial Therapeutic Potential by an Optimized Sample Preparation and Colony PCR Method.

We demonstrate that JCM1395 has the potential to be used for tumor-targeted live bacterial therapeutics. Prior to studying its in vivo biodistribution, a sample preparation method for reliable quantitative analysis of bacteria in biological tissues was required. Gram-positive bacteria have a thick outer layer of peptidoglycans, which hindered the extraction of 16S rRNA genes for colony PCR.

Impact of tumoral structure and bacterial species on growth and biodistribution of live bacterial therapeutics in xenografted tumours.

Live bacterial therapeutics is gaining attention, especially for cancer therapy, because anaerobic bacteria selectively grow inside the solid tumours. However, the effect of tumour structure and bacterial characteristics on the pharmacokinetics of tumours is unclear; therefore, we aimed to elucidate the effects of tumour structure and types of bacteria on tumoral bacterial growth. Using six mouse xenograft models, including stroma-rich tumours similar to clinical tumours, and two models of live bacterial therapeutics, VNP20009 and DH5α, we investigated bacterial growth and distribution in tumours after intravenous administration.

Histone deacetylation regulates nucleotide excision repair through an interaction with the XPC protein.

The XPC protein complex plays a central role in DNA lesion recognition for global genome nucleotide excision repair (GG-NER). Lesion recognition can be accomplished in either a UV-DDB-dependent or -independent manner; however, it is unclear how these sub-pathways are regulated in chromatin. Here, we show that histone deacetylases 1 and 2 facilitate UV-DDB-independent recruitment of XPC to DNA damage by inducing histone deacetylation.

Biosorption-based Cu-labeling of bacteria for pharmacokinetic positron-emission tomography.

Biosorption-based bacterial Cu-labeling and its application in pharmacokinetic positron-emission tomography (PET) were investigated. Both gram-positive and gram-negative bacteria were efficiently labeled with [Cu]Cu ion in saline at room temperature within 5 min. The labeling ratio for Escherichia coli drastically decreased with trypsin pretreatment and the co-presence of excess Cu ion, indicating the existence of specific Cu binding sites on the E.

The potential utility of anterior upper lobe honeycomb-like lesion in interstitial lung disease associated with connective tissue disease.

Background: Interstitial lung disease (ILD) is associated with high morbidity and mortality in patients with connective tissue disease (CTD). Because some patients with CTD overlap present with ILD first, with CTD diagnosed later, specific radiologic signs are needed to help differentiate each CTD or CTD-ILD from idiopathic ILD.

Objectives: To determine whether specific CT findings can help differentiate CTD as rheumatoid arthritis (RA), systemic sclerosis (SSc), or polymyositis/dermatomyositis (PM/DM).

Involvement of Caveolin-1-mediated transcytosis in the intratumoral accumulation of liposomes.

For achieving efficient cancer treatment, it is important to elucidate the mechanism responsible for the accumulation of nanoparticles in tumor tissue. Recent studies suggest that nanoparticles are not delivered merely through gaps between tumor endothelial cells. We previously reported that the maturation of the vascular structure by the vascular endothelial cell growth factor receptor 2 (VEGFR2) using a previously developed siRNA delivery technology (RGD-MEND) significantly enhanced the accumulation of nanoparticles in types of cancers that area vessel-rich (renal cell carcinoma).

Impact of radiological honeycombing in rheumatoid arthritis-associated interstitial lung disease.

Background: Interstitial lung disease (ILD) is the most common and important pulmonary manifestation of rheumatoid arthritis (RA). A radiological honeycomb pattern has been described in diverse forms of ILD that can impact survival. However, the clinical course and sequential radiological changes in the formation of the honeycomb pattern in patients with RA-ILD is not fully understood.

Synergistic Enhancement of Cellular Uptake With CD44-Expressing Malignant Pleural Mesothelioma by Combining Cationic Liposome and Hyaluronic Acid-Lipid Conjugate.

Malignant pleural mesothelioma (MPM) is a highly aggressive form of cancer, with a median survival of less than 1 year. It is well known that the hyaluronan (HA) receptor CD44 is highly expressed by MPM cells and is reported to be correlated with a poor prognosis. We herein report on the development of a new type if drug delivery system against CD44 that involves the use of lipid nanoparticles (LNPs) equipped with a new type of HA derivative.

A lambda-shaped retractor lentis muscle in the yellowfin goby Acanthogobius flavimanus.

We identified a morphologically uncommon piscine retractor lentis muscle in the yellowfin goby Acanthogobius flavimanus. This lentis muscle has a shape similar to the Greek small letter lambda (λ). The two legs of the muscle are attached to the retinal periphery at the ventral eyecup, while the tip is connected to the lens surface by a ligament.

Effective Therapy Using a Liposomal siRNA that Targets the Tumor Vasculature in a Model Murine Breast Cancer with Lung Metastasis.

Although metastatic cancer is a major cause of death for cancer patients, no efficacious treatment for metastasis is available. We previously showed that the growth of a primary tumor could be inhibited by the administration of an anti-angiogenic small interfering RNA (siRNA) that is encapsulated in an RGD peptide-modified lipid nanoparticle (RGD-LNP). We herein report on the delivery of siRNA by an RGD-LNP to the vasculature is also effective for treating metastatic tumors.

The Delivery of Small Interfering RNA to Hepatic Stellate Cells Using a Lipid Nanoparticle Composed of a Vitamin A-Scaffold Lipid-Like Material.

Hepatic stellate cells (HSCs) are responsible for hepatic fibrosis and liver cirrhosis via their ability to produce extracellular matrices such as collagens and elastin. However, a strategy for delivering cargoes to HSCs has not been established yet. We herein report on attempts to deliver small interfering RNA (siRNA) to HSCs using several types of SS-cleavable proton-activated lipid-like materials (ssPalms) that contained myristic acid (ssPalmM) or hydrophobic vitamin A (ssPalmA) and E (ssPalmE) as hydrophobic scaffolds.

Xeroderma pigmentosum group C protein interacts with histones: regulation by acetylated states of histone H3.

In the mammalian global genome nucleotide excision repair pathway, two damage recognition factors, XPC and UV-DDB, play pivotal roles in the initiation of the repair reaction. However, the molecular mechanisms underlying regulation of the lesion recognition process in the context of chromatin structures remain to be understood. Here, we show evidence that damage recognition factors tend to associate with chromatin regions devoid of certain types of acetylated histones.

Modality of tumor endothelial VEGFR2 silencing-mediated improvement in intratumoral distribution of lipid nanoparticles.

The vascular endothelial growth factor (VEGF)-mediated enhancement in vascular permeability is considered to be a major factor in tumor-targeting delivery via the enhanced permeability and retention (EPR) effect. We previously reported that the silencing of the endothelial VEGF receptor (VEGFR2) by a liposomal siRNA system (RGD-MEND) resulted in an enhanced intratumoral distribution of polyethylene glycol (PEG)-modified liposomes (LPs) in a renal cell carcinoma, a type of hypervascularized cancer, although the inhibition of VEGF signaling would be expected to decrease the permeability of the tumor vasculature. We herein report that the enhancement in the intratumoral distribution of LPs by VEGFR2 inhibition was dependent on the vascular type of the tumor (stroma vessel type; SV and tumor vessel type; TV).

Remodeling of the Extracellular Matrix by Endothelial Cell-Targeting siRNA Improves the EPR-Based Delivery of 100 nm Particles.

A number of nano drug delivery systems have recently been developed for cancer treatment, most of which are based on the enhanced permeability and retention effect. The advantages of the enhanced permeability and retention effect can be attributed to immature vasculature. Herein we evaluated the intratumoral distribution of lipid nanoparticles when the VEGF receptor 2 on tumor endothelial cells was inhibited by liposomal siRNA.

Induction of truncated form of tenascin-X (XB-S) through dissociation of HDAC1 from SP-1/HDAC1 complex in response to hypoxic conditions.

XB-S is an amino-terminal truncated protein of tenascin-X (TNX) in humans. The levels of the XB-S transcript, but not those of TNX transcripts, were increased upon hypoxia. We identified a critical hypoxia-responsive element (HRE) localized to a GT-rich element positioned from -1410 to -1368 in the XB-S promoter.