Locally advanced solitary fibrous tumour of the prostate.

Solitary fibrous tumours (SFTs) are rare mesenchymal neoplasms composed of spindle cells, most often occurring in the pleura. SFTs arising from the prostate are exceptionally rare, with only around 40 cases reported in literature to date. We report a man in his 60s who was referred to our clinic for elevated prostate-specific antigen and presented with mild obstructive lower urinary tract and defecatory symptoms. Prostate needle-core biopsy revealed neoplastic spindle cells that strongly expressed CD34. Cross-sectional imaging demonstrated a 12 cm locally advanced heterogeneous prostate mass with intravesical extension and mass effect on the anterior rectum. Radical cystoprostatectomy with orthotopic neobladder reconstruction was performed, and the diagnosis of primary prostatic SFT was made based on histological characteristics and immunophenotyping. We present diagnostic, clinical management and prognostic considerations in patients with primary prostatic SFT.

Transudative Malignancy: Uncommon and Real.

Light's criteria are the cornerstone to differentiate exudates from transudates. The traditional literature states that malignant pleural effusions are rarely transudative; therefore, cytology tends to be low yield and not a cost-effective decision. This case describes an 82-year-old female who developed a transudative pleural effusion despite having an underlying malignancy, highlighting the importance of integrating clinical judgment into pursuing thoracentesis with the cytological examination.

Genome-wide DNA methylation profile of peripheral blood lymphocytes from subjects with nonsteroidal anti-inflammatory drug-induced respiratory diseases.

BACKGROUND: Significant changes in CpG methylation have been identified in nasal polyps, which are the main targets of nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD); however, these polyps are composed of various cellular components. In the present study, whole-genome CpG methylation in peripheral blood lymphocytes (PBLs) was analyzed to define the epigenetic changes in lymphocytes, which are the primary immune cells involved in NERD. MATERIALS AND METHODS: Genomic DNA from peripheral blood mononuclear cells from 27 NERD and 24 aspirin-tolerant asthma (ATA) was subjected to bisulfate conversion and a methylation array. Quantitative CpG methylation, the ß-values as a quantitative measure of DNA methylation, in lymphocytes were calculated after adjustments for cellular composition. RESULTS: Fifty-six hypermethylated and three hypomethylated differentially methylated CpGs (DMCs) in PBLs in the NERD compared with ATA. The top 10 CpG loci predicted the methylation risk score, with a positive predictive value of 91.3%, a negative predictive value of 81.5% and an accuracy of 84.3%. As demonstrated in the nasal polyps, 30 DMCs were predicted to bind to the following 10 transcription factors, ranked in descending order: AP-2alphaA, TFII-1, STAT4, FOXP3, GR, c-Est-1, E2F-1, XBP1, ENKTF-1 and NF-1. Gene ontology analysis identified 13 categories such as regulation of T-helper 17 cell differentiation, including SMAD7 and NFKBIZ. PBLs in NERD contained no DMCs in genes associated with the prostaglandin and leukotriene pathways, which were found in ATA. CONCLUSION: PBLs in NERD form a unique pattern of DNA CpG methylation, and the combined analysis may provide predictive values for NERD.

Synthesis and biological activity of selenopsammaplin A and its analogues as antitumor agents with DOT1L inhibitory activity.

Disruptor of telomeric silencing-1 like (DOT1L) is a histone H3 methyltransferase which specifically catalyzes the methylation of histone H3 lysine-79 residue. Recent findings demonstrate that DOT1L is abnormally overexpressed and the upregulated DOT1L evokes the proliferation and metastasis in human breast cancer cells. Therefore, the DOT1L inhibitor is considered a promising strategy to treat breast cancers. Non-nucleoside DOT1L inhibitors, selenopsammaplin A and its analogues, were firstly reported in the present study. Selenopsammaplin A was newly designed and synthesized with 25% overall yield in 8 steps from 3-bromo-4-hydroxybenzaldahyde, and thirteen analogues of selenopsammaplin A were prepared for structure-activity relationship studies of their cytotoxicity against cancer cells and inhibitory activity toward DOT1L for antitumor potential. All synthetic selenopsammaplin A analogues exhibited the higher cytotoxicity compared to psammaplin A with up to 6 - 60 times depending on cancer cells, and most analogues showed significant inhibitory activities against DOT1L. Among the prepared analogues, the phenyl analogue (10) possessed the most potent activity with both cytotoxicity and inhibition of DOT1L. Compound 10 also exhibited the antitumor and antimetastatic activity in an orthotopic mouse metastasis model implanted with MDA-MB-231 human breast cancer cells. These biological findings suggest that analogue 10 is a promising candidate for development as a cancer chemotherapeutic agent in breast cancers.

Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.

ETHNOPHARMACOLOGICAL RELEVANCE: Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA). In the present study, we investigated the anti-osteoporotic potential of harpagide and its underlying mechanism of action in in vitro cell culture and in vivo bone loss animal models. MATERIAL AND METHODS: Harpagide was obtained from the alkalic hydrolysis of harpagoside, a major constituent of H. procumbens var. sublobatum Analysis of biomarkers for bone formation in osteoblastic MC3T3-E1 cells and bone resorption in osteoclast cells derived from mouse bone marrow cells was performed to evaluate the mechanism of action. The protective activity of harpagide against bone loss was also evaluated in ovariectomized (OVX) mouse model. RESULTS: Harpagide improved bone properties by stimulating the process of differentiation and maturation of osteoblast cells and suppressing the process of RANKL-induced differentiation of osteoclast cells. In OVX-induced bone loss mouse model, oral administration of harpagide significantly improved recovery of bone mineral density, trabecular bone volume, and trabecular number in the femur. Harpagide also prevented increase of trabecular separation and structure model index induced by OVX. Harpagide effectively inhibited the serum levels of biochemical markers of bone loss, including alkaline phosphatase, osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase. CONCLUSION: Taken together, the present study demonstrates that harpagide has a potential for prevention of bone loss in OVX mice by regulating the stimulation of osteoblast differentiation and the suppression of osteoclast formation. Therefore, these findings suggest that harpagide might serve as a bioactive compound derived from H. procumbens var. sublobatum for improvement of age-dependent bone destruction disease.

Expression of Fas and Fas ligand in primary cutaneous squamous cell carcinoma in association with grade of tumor differentiation.

BACKGROUND: The aim of this study was to evaluate whether Fas (CD95) and Fas ligand (FasL) immunoreactivity in cutaneous squamous cell carcinoma (SCC) are correlated with grade of tumor differentiation. METHODS: A total of 31 cutaneous SCC specimens excised during 1997-2004 were collected from the four branch hospitals of the Catholic University of Korea. A tissue microarray technique was used for immunohistochemical staining. Expression of Fas and FasL was evaluated in correlation with the grade of tumor differentiation. Statistical analysis was performed using Fisher's exact test and exact trend test. RESULTS: Six of 31 SCCs exhibited strong (+++) intensity for Fas immunostaining, and all of these were well differentiated. Five of 31 SCCs exhibited strong (+++) intensity for FasL staining; all of these were moderately or poorly differentiated. CONCLUSIONS: Fas was expressed more strongly in well-differentiated SCCs than in poorly differentiated tumors. FasL was expressed more strongly in moderately and poorly differentiated tumors. These findings indicate that Fas and FasL play important roles in immune surveillance and grade of differentiation in SCC.

Neuroprotective effects of an herbal medicine, Yi-Gan San on MPP+/MPTP-induced cytotoxicity in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: A traditional herb, Yi-Gan San, has been widely used for the management of neurodegenerative disorders in traditional East Asian Medicine. AIM OF THE STUDY: The present study investigated the neuroprotective effects of Yi-Gan San in 1-methyl-4-phenylpyridine/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced cytotoxicity in vitro and in vivo and sought to clarify its underlying mechanisms. MATERIALS AND METHODS: The effect of Yi-Gan San on 1-methyl-4-phenylpyridine was measured in terms of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays, caspase-3 activity, and western blot analysis of phosphorylated Akt, one of the survival-related signaling proteins in SH-SY5Y cells. The effects of Yi-Gan San were also confirmed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonian mouse model using a rotarod test and tyrosine hydroxylase-immunohistochemistry. RESULTS: Pretreatment of Yi-Gan San with 1-methyl-4-phenylpyridine showed a significant protective effect on SH-SY5Y cells and significantly decreased the level of caspase-3 activity compared to the values for the 1-methyl-4-phenylpyridine-treated cells. This process increased the protein expressions of phosphorylated Akt, and an inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt, LY294002, significantly decreased this protective effect of Yi-Gan San. In the mouse Parkinson's disease model, treatment with Yi-Gan San also significantly improved motor functioning and prevented dopaminergic loss related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine challenge. CONCLUSION: Using both in vitro and in vivo methods, this study revealed that Yi-Gan San has neuroprotective effects and rescues dopaminergic neurons from 1-methyl-4-phenylpyridine/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity, possibly via the PI3K/Akt pathway.

Iron oxide-based nanomagnets in nanomedicine: fabrication and applications.

Iron oxide-based nanomagnets have attracted a great deal of attention in nanomedicine over the past decade. Down to the nanoscale, superparamagnetic iron oxide nanoparticles can only be magnetized in the presence of an external magnetic field, which makes them capable of forming stable colloids in a physio-biological medium. Their superparamagnetic property, together with other intrinsic properties, such as low cytotoxicity, colloidal stability, and bioactive molecule conjugation capability, makes such nanomagnets ideal in both in-vitro and in-vivo biomedical applications. In this review, a chemical, physical, and biological synthetic approach to prepare iron oxide-based nanomagnets with different physicochemical properties was illustrated and compared. The growing interest in iron oxide-based nanomagnets with multifunctionalities was explored in cancer diagnostics and treatment, focusing on their combined roles in a magnetic resonance contrast agent, hyperthermia, and magnetic force assisted drug delivery. Iron oxides as magnetic carriers in gene therapy were reviewed with a focus on the sophisticated design and construction of magnetic vectors. Finally, the iron oxide-based nanomagnet also represents a very promising tool in particle/cell interfacing in controlling cellular functionalities, such as adhesion, proliferation, differentiation, and cell patterning, in stem cell therapy and tissue engineering applications.

Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid.

Pseudomonas aeruginosa is an important opportunistic pathogen that can cause chronic and often life-threatening infections of the respiratory tract, particularly in individuals with cystic fibrosis (CF). Because infections with P. aeruginosa remain the major cause of the high morbidity and mortality of CF, a vaccine against P. aeruginosa would be very useful for preventing this disorder. The outer membrane protein F (OprF) of P. aeruginosa is a promising vaccine candidate and various B cell epitopes within OprF have been identified. Given that adenovirus (Ad) vectors have strong immunogenic potential and can function as adjuvants for genetic vaccines, the present study evaluates the immunogenic and protective properties of a novel replication-deficient Ad vector in which the Ad hexon protein was modified to include a 14-amino acid epitope of P. aeruginosa OprF (Epi8) in loop 1 of the hypervariable region 5 of the hexon (AdZ.Epi8). Immunization of C57BL/6 mice with AdZ.Epi8 resulted in detectable serum anti-P. aeruginosa and anti-OprF humoral responses. These responses were haplotype dependent, with higher serum anti-OprF titers in CBA mice than in BALB/c or C57BL/6 mice. AdZ.Epi8 induced Epi8-specific IFN-gamma-positive CD4 and CD8 T cell responses and resulted in protection against a lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeated administration of AdZ.Epi8 resulted in boosting of the anti-OprF humoral and anti-Epi8 cellular response, whereas no boosting effect was present in the response against the transgene beta-galactosidase. These observations suggest that Ad vectors expressing pathogen epitopes in their capsid will protect against an extracellular pathogen and will allow boosting of the epitope-specific humoral response with repeated administration, a strategy that should prove useful in developing Ad vectors as vaccines where humoral immunity will be protective.