Synthesis and evaluation of novel dolastatin 10 derivatives for versatile conjugations.

Dolastatin 10 (1) is a highly potent cytotoxic microtubule inhibitor (cytotoxicity IC < 5.0 nM) and several of its analogs have recently been used as payloads in antibody drug conjugates. Herein, we describe the design and synthesis of a series of novel dolastatin 10 analogs useful as payloads for conjugated drugs.

Novel pegylated interferon-β as strong suppressor of the malignant ascites in a peritoneal metastasis model of human cancer.

Malignant ascites manifests as an end-stage event during the progression of a number of cancers and lacks a generally accepted standard therapy. Interferon-β (IFN-β) has been used to treat several cancer indications; however, little is known about the efficacy of IFN-β on malignant ascites. In the present study, we report on the development of a novel, engineered form of human and murine IFN-β, each conjugated with a polyethylene glycol molecule (PEG-hIFN-β and PEG-mIFN-β, respectively).

Interferon-β Mediates Signaling Pathways Uniquely Regulated in Hepatic Stellate Cells and Attenuates the Progression of Hepatic Fibrosis in a Dietary Mouse Model.

The results of clinical and experimental studies suggest that type I interferons (IFNs) may have direct antifibrotic activity in addition to their antiviral properties. However, the mechanisms are still unclear; in particular, little is known about the antifibrotic activity of IFN-β and how its activity is distinct from that of IFN-α. Using DNA microarrays, we demonstrated that gene expression in TWNT-4 cells, an activated human hepatic stellate cell line, was remarkably altered by IFN-β more than by IFN-α.

RECOT: a tool for the coordinate transformation of next-generation sequencing reads for comparative genomics and transcriptomics.

Background: The whole-genome sequences of many non-model organisms have recently been determined. Using these genome sequences, next-generation sequencing based experiments such as RNA-seq and ChIP-seq have been performed and comparisons of the experiments between related species have provided new knowledge about evolution and biological processes. Although these comparisons require transformation of the genome coordinates of the reads between the species, current software tools are not suitable to convert the massive numbers of reads to the corresponding coordinates of other species' genomes.

Interferon-beta reduces the mouse liver fibrosis induced by repeated administration of concanavalin A via the direct and indirect effects.

Type I interferons (IFNs), IFN-alpha and IFN-beta, are widely used for treating chronic hepatitis C. Although retrospective studies have suggested that type I IFNs have direct antifibrotic effects, little is known about these mechanisms. The present study was designed to clarify the preventive mechanisms of type I IFNs in the progression of fibrosis for the establishment of a more effective therapy.

The combination of type I interferon and ribavirin has an inhibitory effect on mouse hepatitis virus infection.

Aim: To determine the differences in efficacy between therapy using IFN-beta and ribavirin, and using IFN-alpha and ribavirin.

Methods: We studied the effect of combination therapy consisting of IFN-beta and ribavirin on mouse hepatitis virus (MHV) infection in mice.

Results: Combination treatment of ribavirin and IFN-alpha was more effective than IFN-alpha mono-treatment in the MHV-mouse system, and combination treatment with ribavirin and IFN-beta was more effective than IFN-beta mono-treatment in the MHV-mouse system.

Interferon-{beta} inhibits bleomycin-induced lung fibrosis by decreasing transforming growth factor-{beta} and thrombospondin.

Pulmonary fibrosis is the result of abnormal processes of repair that occur after lung injury. Transforming growth factor (TGF)-beta is a key molecule in the progression of pulmonary fibrosis. Although clinical use of interferon (IFN)-beta did not improve survival in patients with idiopathic pulmonary fibrosis, because some preclinical studies have suggested that IFN-beta is a potent inhibitor of fibrogenesis, beneficial effects of IFN-beta have been expected.

Relevance of c-erbB2, PLU-1 and survivin mRNA expression to diagnostic assessment of breast cancer.

The positivity rates of mRNA expression in breast cancer of the tumor-related genes for c-erbB2, PLU-1 and survivin are unclear. We quantitatively analyzed tissue samples from 39 breast cancers and non-cancerous parts of the same specimens for the above three mRNAs using a TaqMan reverse transcription-polymerase chain reaction (RT-PCR). Using the mean + 2SD of non-cancerous sample as a cut-off value, the positivity rates of the tumors for c-erbB2, PLU-1 and survivin were 20.

Survivin mRNA expression in patients with breast cancer.

We measured survivin mRNA expression in breast cancers using a fluorogenically detected reverse transcription-polymerase chain reaction, seeking relationships between expression and clinical and histological variables. The mean relative expression of survivin mRNA was 0.347+/-0.