A new antisense oligonucleotide delivery system based on self-assembled ODN-PEG hybrid conjugate micelles.

The conjugate of antisense c-raf oligonucleotide (ODN) and poly(ethylene glycol) (PEG) was synthesized for intracellular ODN delivery. When combined with polyethylenimine (PEI), the ODN-PEG conjugate self-associated to form polyelectrolyte complex micelles in aqueous solution. The effective hydrodynamic diameter of the micelles was ca. 70 nm with a narrow size distribution. Flow cytometry analysis indicated that the cellular uptake of the micelles by A2780 cells was much higher than that of ODN alone. The micelles also showed a superior antiproliferative activity against ovarian cancer cells in vitro and in vivo.     

Celecoxib induces functional recovery after intracerebral hemorrhage with reduction of brain edema and perihematomal cell death.

The selective cyclooxygenase-2 (COX-2) inhibitor has been reported to have antiinflammatory, neuroprotective, and antioxidant effects in ischemia models. In this study, the authors examined whether a selective COX-2 inhibitor (celecoxib) reduces cerebral inflammation and edema after intracerebral hemorrhage (ICH), and whether functional recovery is sustained with longer treatment. ICH was induced using collagenase in adult rats. Celecoxib (10 or 20 mg/kg) was administered intraperitoneally 20 minutes, 6 hours, and 24 hours after ICH and then daily thereafter. Seventy-two hours after ICH induction, the rats were killed for histologic assessment and measurement of brain edema and prostaglandin E2. Behavioral tests were performed before and 1, 7, 14, 21, and 28 days after ICH. The brain water content of celecoxib-treated rats decreased both in lesioned and nonlesioned hemispheres in a dose-dependent manner. Compared with the ICH-only group, the number of TUNEL-positive, myeloperoxidase-positive, or OX42-positive cells was decreased in the periphery of hematoma and brain prostaglandin E2 level was reduced in the celecoxib-treated group. Celecoxib-treated rats recovered better by the behavioral tests at 7 days after ICH throughout the 28-day period, and the earlier the drug was administered, the better the functional recovery. Evidence of similar effects in an autologous blood-injected model showed that direct collagenase toxicity was not the major cause of inflammation or cell death. These data suggest that celecoxib treatment after ICH reduces prostaglandin E2 production, brain edema, inflammation, and perihematomal cell death in the perihematomal zone and induces better functional recovery.     

Solitary Small Hepatic Angiosarcoma: Initial and Follow-up Imaging Findings

We report an uncommon case of solitary, small hepatic angiosarcoma that was initially considered as a hemangioma. We present the imaging findings, with an emphasis on the initial and follow-up CT and MR findings, as well as report on the more suggestive findings of angiosarcoma than those of a hemangioma.     

Poly(L-lysine)-g-poly(D,L-lactic-co-glycolic acid) micelles for low cytotoxic biodegradable gene delivery carriers.

Poly(lactic-co-glycolic acid) (PLGA)-grafted poly(L-lysine) (PLL) (PLL-g-PLGA) was synthesized to demonstrate its micelle-forming property in an aqueous solution. The micelles were used as a gene delivery carrier. The hydrodynamic diameter of PLL-g-PLGA micelles in an aqueous solution was ca. 149 nm with a narrow size distribution. Critical micelle concentration (cmc) was 9.6 mg/l. The PLL-g-PLGA micelles could be used to produce compact nanoparticulate complexes with plasmid DNA, which could efficiently protect the complexed DNA from enzymatic degradation by DNase I. The micelle/DNA complexes had highly compacted structure sized between 200-300 nm with a positive surface charge value. The PLL-g-PLGA micelles exhibited much higher transfection efficiency with lower cytotoxicity than PLL. Here, we demonstrated that biodegradable and cationic PLL-g-PLGA micelles could be used as an effective DNA condensation carrier for gene delivery system.     

Cyclin E, p27 and mutant p53 do not predict the prognosis in AJCC stage II colorectal carcinomas.

BACKGROUND/AIMS: Carcinogenesis is characterized by the abnormal regulation of cell cycle. The abnormal expression of the regulators of cell cycle may be related to the prognosis. Since the clinical significance of the expression of the three proteins in colorectal carcinomas is still controversial, we evaluated the prognostic value of the expression of cyclin E, p27 and mutant p53 in stage II colorectal cancer. METHODS: The expression levels of cyclin E, p27 and mutant p53 proteins in 41 patients with stage II colorectal carcinomas were analyzed by immunohistochemistry. RESULTS: In the univariate analysis, the level of CEA at diagnosis was associated with disease relapse. In the multivariate analysis, the clinicopathological variables such as age, gender, site of primary tumor, tumor size, state of tumor differentiation and preoperative plasma CEA level were not associated with disease relapse. When Kaplan-Meier survival curves were constructed to determine the prognosis, cyclin E, p27 and mutant p53 expressions did not predict poor prognosis. CONCLUSIONS: Our results suggested that the expression of cyclin E, p27 and mutant p53 proteins did not predict the clinical outcome in the stage II colorectal carcinomas.     

前额迟发性小汗腺血管瘤性错构瘤

一71岁韩国男性前额出现孤立的红色斑块。该斑块出现已有1年,并缓慢增大。体检发现前额上正中线部有一轻微隆起的、1.5cm×1.5cm红色斑块。体力活动或情绪应激反应均不诱发该斑块出汗。皮损无疼痛或触痛。患者前额部无外伤史。皮损组织病理检查示外分泌腺数目增加,真皮深部和皮     

A case of Non-Hodgkin's lymphoma in a patient with Crohn's disease]

Although adenocarcinoma is a well known complication of chronic inflammatory bowel disease, primary gastrointestinal lymphoma occurring in Crohn's disease is rare. A 40-year-old man with 10 year-history of Crohn's disease had multiple longitudinal ulcerative lesions on descending colon in follow-up colonoscopic examination. Microscopic examination of proximal descending colon revealed peripheral T cell lymphoma and other site of the descending colon was consistent with Crohn's disease. The patient reached complete remission of malignant lymphoma after three cycles of combined chemotherapy. He has been well for 10 months with sulfasalazine maintenance therapy but was admitted to the hospital due to spontaneous bowel perforation of ascending colon. Right hemicolectomy was done, but the patient died of post-surgical recurrent mesenteric abscess and sepsis. To the best of our knowledge, this is the first case of Non-Hodgkin's lymphoma complicating Crohn's disease in Korea which was confirmed by immunohistochemical studies.     

Enhanced expression of adenovirus-mediated sodium iodide symporter gene in MCF-7 breast cancer cells with retinoic acid treatment.

Increased expression of the sodium iodide symporter (NIS) is required for effective radioiodine treatment and reporter gene imaging of breast cancer. We investigated the effect of retinoic acid on adenovirus-mediated expression of the human NIS gene in the MCF-7 breast cancer cell line. METHODS: The MCF-7 cell line was infected with recombinant adenovirus carrying the human NIS gene (Rad-NIS). Levels of NIS messenger RNA (mRNA) and protein expression and radioiodine ((125)I) uptake were measured to evaluate adenovirus-mediated NIS gene expression in wild-type and Rad-NIS-infected MCF-7 cells after treatment with all-trans-retinoic acid (ATRA; 10(-8)-10(-6) mol/L). RESULTS: The transduction efficiency of adenovirus in MCF-7 cells at a multiplicity of infection (MOI) of 50 was >60%. After incubation with 10(-6) mol/L ATRA, the mRNA level in Rad-NIS-infected MCF-7 cells increased to 118.5 times that of wild-type MCF-7 cells, whereas the mRNA level in wild-type MCF-7 cells showed only a 2.1-fold increase. Western blot, immunocytochemical staining, and flow cytometry analyses showed that NIS protein expression in MCF-7 cells infected with Rad-NIS increased after ATRA treatment. With ATRA treatment, the amount of (125)I uptake increased in a dose-dependent manner (P < 0.001). The (125)I uptake in wild-type MCF-7 cells increased 3.1-, 5.5-, and 7.6-fold with treatment with 10(-8), 10(-7), and 10(-6) mol/L ATRA, respectively. Rad-NIS-infected cells showed a 4.0-fold increase in (125)I uptake. Treatment of Rad-NIS-infected cells with 10(-8), 10(-7), and 10(-6) mol/L ATRA increased (125)I uptake by 4.9-, 8.2-, and 27.6-fold, respectively, compared with wild-type MCF-7 cells. The level of NIS expression in Rad-NIS-infected MCF-7 cells treated with 10(-6) mol/L ATRA (245.0 +/- 13.7 pmol/10(6) cells) was much greater than the sum of the expression levels seen in ATRA-treated wild-type cells and Rad-NIS-infected wild-type cells. CONCLUSION: Retinoic acid increases adenovirus-mediated NIS expression in MCF-7 cells. Our results indicate that improved efficiency of NIS gene therapy or reporter imaging in breast cancer may be possible with retinoic acid treatment.     

The study of diethylstilbestrol toxic effect in the mouse sertoli cell line by comparison of miRNA and mRNA expression

It is important to acknowledge the harmful effects of environmental chemicals in human’s lives. The toxic effects of Diethylstilbestrol (DES), one of the endocrine-disrupting chemicals (EDCs), have been documented in many studies. As expected, DES affect male gendal hormone as well as female’s; therefore, epigenetic study should be considered. In this study, microarray technology was used to study harmful effects on the level of genomics, and here, two types of microarray chips- the Agilent mouse genome 4 × 44 K array for gene expression profiling and the Agilent mouse miRNA v13 for miRNA expression profiling-was used to study the relation between gene and miRNA expression profiles. As a result, we identified 4 miRNAs (miR 203, 350, 421, and 466i) that were similarly expressed at 3 hrs and 24 hrs of DES treat times. Twenty one genes matched between predicted target for 4 miRNAs and 118 genes expressed similarly. These genes have functions related to cell differentiation and cell cycle. Therefore, DES affects cellular function and induces toxicity in TM4 cells. In future studies, it is necessary to find more related functions and mechanisms of DES in the system.     

The application of molecular techniques to solid tumors

Recent developments in the field of molecular biology including the sequencing of the human genome and related high throughput methodologies are presenting the diagnostic pathologist with new opportunities to expand our understanding of human disease. These techniques enable the comprehensive assessment of molecular alterations with cell populations of interest, including cancer. It will be necessary for the diagnostic pathologist to become familiar with these techniques to effectively translate their potential into the clinical environment.