Early onset multiple myeloma in a patient with systemic lupus erythematosus: a case report and literature review

Patients with systemic lupus erythematosus (SLE) are at increased risk for various plasma cell dyscrasias, but the coexistence of SLE and multiple myeloma (MM) are rarely reported to date. Due to the rarity, the clinical features of MM associated with SLE have not been elucidated, and the pathogenesis under this association remains unclear. In this report, we investigate a 31-year-old woman with 5-year history of SLE, who is diagnosed as IgA λ-type MM with multiple lymph node involvement. We discuss the clinical features of MM in SLE by reviewing previous cases and possible mechanisms connecting the two conditions.     

Application of the combined use of ultrasonic homogenization and electro-spraying in the formation of nano carrier systems

Chitosan-coated nano-liposomes containing etofenprox were prepared by ultrasonic homogenization (UH) and a combined use of UH and electro-spraying. The physicochemical properties of the resulting samples were examined and compared. The two methods yielded similar values and tendencies, except for encapsulation efficiency that differed by an average of 15%. In the coating process, as the chitosan concentration increased (0.1-0.5%, w/v) and the degree of deacetylation increased (chitosans A, B and C), the surface charge of the nano carrier likewise increased and carrier size distribution was altered. The encapsulation efficiency as measured by gas chromatography decreased slightly with the increasing chitosan concentration (0.1-0.5%, w/v). The results indicate that diverse preparation conditions could affect the physicochemical properties of the resulting nano carrier systems.     

Quantitative determination of daumone in rat plasma by liquid chromatography-mass spectrometry

Daumone, 6-(3,5-dihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-heptanoic acid is a pheromone secreted by Caenorhabditis elegans, and has been known as a pivotal regulator of chemosensory processes in development and ageing. A quantification method using mass spectrometry was developed for the determination of daumone in rat plasma. After simple protein precipitation with acetonitrile including an internal standard, the analytes were chromatographed on a reversed-phase column and detected by liquid chromatography/tandem mass spectrometry with electrospray ionization. The accuracy and precision of the assay were in accordance with FDA regulations for validation of bioanalytical methods. This method was applied to measure the plasma daumone concentrations after a single intravenous administration of daumone in rats.     

Discovery and applications of disulfide-rich cyclic peptides

Cyclic peptides typically have much higher stability and improved biopharmaceutical properties over their linear counterparts. Our work focuses on the discovery of naturally occurring disulfide-rich cyclic peptides and their applications in drug design. These peptides provide a design basis for re-engineering natural acyclic peptides to improve their biopharmaceutical properties by chemically linking their termini. Here we describe examples of the discovery of the cyclotide family of peptides, their chemical re-engineering to introduce desired pharmaceutical activities, studies of their biopharmaceutical properties and applications of cyclization technologies to naturally occurring toxins, including conotoxins and scorpion toxins. In the case of the conotoxin Vc1.1, we produced an orally active peptide with potential for the treatment of neuropathic pain by cyclising the native peptide. In the case of the scorpion toxin chlorotoxin, a cyclised derivative had improved biopharmaceutical properties as a tumour imaging agent over the naturally occurring linear chlorotoxin. Ongoing chemical and structural studies of these classes of disulfide-rich peptides promise to increase their value for use in dissecting biological processes in plants and mammals while also providing leads to new classes of biopharmaceuticals.     

The apoptotic effects of the flavonoid N101-2 in human cervical cancer cells

This study evaluated the anti-cancer effects of a naringenin derivative in human cervical cancer cells. In this study, a synthesized naringenin derivative, diethyl 5,7,4'-trihydroxy flavanone N-phenyl hydrazone (N101-2), inhibited cervical cancer cell growth, whereas naringenin itself exhibited no anti-cancer activity. N101-2 treatment inhibited cancer cell viability in a dose- and time-dependent manner through cell cycle arrest at sub-G1 phase, accompanied by an increase in apoptotic cell death. Expression of cyclins and ppRB was down-regulated, whereas that of CDK inhibitors and p53 increased upon N101-2 treatment. Meanwhile, we detected processing of caspases-8, -9, and -3, cleavage of PARP, as well as Bax up-regulation, which indicates activation of mitochondria-emanated intrinsic apoptosis signaling. Treatment with caspase-8 and -3 inhibitors also recovered cell cycling, and Fas/FasL expression increased in N101-2-treated cervical cancer cells, suggesting that Fas-mediated extrinsic apoptosis signaling was also activated. The tumor suppressor PTEN and its upstream regulator PPARγ were up-regulated with coincident inhibition of PI3K and phospho-Akt after N101-2 treatment. Taken together, we could conclude that N101-2 induces apoptosis by arresting the cell cycle at sub-G1 phase, activating mitochondria-emanated intrinsic and Fas-mediated extrinsic signaling pathways, and inhibiting the PI3K/AKT pathway in CaSki and SiHa human cervical cancer cells.     

Multi-core vesicle nanoparticles based on vesicle fusion for delivery of chemotherapic drugs

The Pluronic nanoparticles (NPs) composed of Pluronic (F-68) and liquid polyethylene glycol (PEG, molecular wt: 400) containing docetaxel (DTX) were stabilized with the vesicle fusion. When DTX-loaded Pluronic NPs were mixed with vesicles in the aqueous medium, DTX-loaded Pluronic NPs were incorporated into vesicles to form multi-core vesicle NPs. The morphology and size distribution of multi-core vesicle NPs were observed using FE-SEM, cryo-TEM and a particle size analyzer. To apply multi-core vesicle NPs as a delivery system for DTX, a model anti-cancer drug, the release pattern of DTX was observed and the tumor growth was monitored by injecting the DTX-loaded multi-core vesicle NPs into the tail veins of tumor-bearing mice. We also evaluated the time-dependent excretion profile, in?vivo biodistribution, circulation time, and tumor targeting capability of multi-core vesicle NPs using a non-invasive live animal imaging technology.     

Molecular identification and expression analysis of a novel tumor necrosis factor receptor from the black rockfish, Sebastes schlegelii

Members of the tumor necrosis factor (TNF) and TNF receptor (TNFR) superfamilies play crucial roles in both innate and adaptive immunity. In the present study, we isolated the full-length cDNA for black rockfish (Sebastes schlegelii) TNFR (BrTNFR). This cDNA is 2405 bp in length and contains a 939-bp open reading frame, a 27-bp 5′ untranslated region, and a 1439-bp 3′ untranslated region including a polyadenylation signal (AATAAA) and polyadenylation site. The 313-amino-acid predicted BrTNFR sequence is homologous to other TNFR sequences, contains four cysteine-rich domains and a death-effector domain (DED), and lacks a transmembrane region. Expression of BrTNFR mRNA was detected in eight different tissues from healthy black rockfish and was highest in peripheral blood lymphocytes and gills. In analyses of mitogen-stimulated BrTNFR expression in peripheral blood lymphocytes, expression of BrTNFR mRNA was observed between 1 and 24 h after stimulation with lipopolysaccharide, concanavalin A/phorbol myristate acetate, or poly I:C. Although the data suggest that BrTNFR represents an ancestral member of the TNFR superfamily, the orthology of TNFR in teleost fish is difficult to establish because few TNFRs have been identified in these species.     

Extracellular proteinase formation in carbon starving Aspergillus nidulans cultures--physiological function and regulation

Extracellular proteinase formation in carbon depleted cultures of the model filamentous fungus Aspergillus nidulans was studied to elucidate its regulation and possible physiological function. As demonstrated by gene deletion, culture optimization, microbial physiological and enzymological experiments, the PrtA and PepJ proteinases of A. nidulans did not appear to play a decisive role in the autolytic decomposition of fungal cells under the conditions we tested. However, carbon starvation induced formation of the proteinases observable in autolytic cultures. Similar to other degradative enzymes, production of proteinase was regulated by FluG-BrlA asexual developmental signaling and modulated by PacC-dependent pH-responsive signaling. Under the same carbon starved culture conditions, alterations of CreA, MeaB or heterotrimeric G protein mediated signaling pathways caused less significant changes in the formation of extracellular proteinases. Taken together, these results indicate that while the accumulation of PrtA and PepJ is tightly coupled to the initiation of autolysis, they are not essential for autolytic cell wall degradation in A. nidulans. Thus, as Aspergillus genomes contain a large group of genes encoding proteinases with versatile physiological functions, selective control of proteinase production in fungal cells is needed for the improved industrial use of fungi.     

Oncogenic anaplastic lymphoma kinase (ALK) mutation in neuroblastomas and other pediatric tumors

Neuroblastoma (NB) is one of the most common malignant pediatric tumors that show aggressive behavior. Most advanced-stage NBs have proven refractory to many treatment modalities, and a fundamental alternative therapy, such as inhibition of biological pathways, is now being explored. Anaplastic lymphoma kinase (ALK) has recently been identified as an activation mutation in familial or high-risk sporadic NBs. We examined the prevalence of the ALK mutation in 54 NB cases (23 pre-treatment cases and 31 cases for which specimens were available before and after treatment) and the presence of the ALK mutation in various pediatric tumors. We detected the ALK mutation (F1174C and R1275Q) in 2 (3.7%) of the 54 NB specimens. Both cases showed poorly differentiated and advanced-stage NBs. No ALK mutations were detected in other pediatric tumors. The frequency of the ALK mutation was somewhat lower than that expected in Korean patients with NBs. The mutation detected in the present study was one of the hotspot mutations, including positions of F1174 and R1275 reported previously. The results of the present study suggest the possibility of potential roles of ALK inhibitors in the therapeutics of a small population of neuroblastoma carrying mutated ALK kinases.