Valproic Acid Downregulates the Expression of MGMT and Sensitizes Temozolomide-Resistant Glioma Cells

Temozolomide (TMZ) has become a key therapeutic agent in patients with malignant gliomas; however, its survival benefit remains unsatisfactory. Valproic acid (VPA) has emerged as an anticancer drug via inhibition of histone deacetylases (HDACs), but the therapeutic advantages of a combination with VPA and TMZ remain poorly understood. The main aim of the present study was to determine whether an antitumor effect could be potentiated by a combination of VPA and TMZ, especially in TMZ-resistant cell lines. A combination of VPA and TMZ had a significantly enhanced antitumor effect in TMZ-resistant malignant glioma cells (T98 and U138). This enhanced antitumor effect correlated with VPA-mediated reduced O6-methylguanine-DNA methyltransferase (MGMT) expression, which plays an important role in cellular resistance to alkylating agents. In vitro, the combination of these drugs enhanced the apoptotic and autophagic cell death, as well as suppressed the migratory activities in TMZ-resistant cell lines. Furthermore, in vivo efficacy experiment showed that treatment of combination of VPA and TMZ significantly inhibited tumor growth compared with the monotherapy groups of mice. These results suggest that the clinical efficacy of TMZ chemotherapy in TMZ-resistant malignant glioma may be improved by combination with VPA

Inflammatory Myofibroblastic Tumor of the Kidney Misdiagnosed as Renal Cell Carcinoma

The inflammatory myofibroblastic tumor (IMT), also knowns as inflammatory pseuduotumor, is a soft tissue lesion of unknown etiology. In the urogenital tract, IMT mainly affects the urinary bladder or prostate, but rarely the kidney. It has been considered as a nonneoplastic reactive inflammatory lesion, but nowadays, it is regarded as a neoplasm due to its high recurrence rate and metastasis. We describe a case of a 61-yr-old woman that had originally been misdiagnosed as renal cell carcinoma, which was pathologically revealed to be an IMT

Association between prostatic 18F-FDG uptake and lower urinary tract symptoms assessed by International Prostate Symptom Score

PURPOSEInflammation is known to induce prostatic growth and lower urinary tract symptoms (LUTS) progression in patients with benign prostatic hyperplasia (BPH), but clinical indicators for intraprostatic inflammation other than biopsy have not yet been established. While 2-deoxy- 2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is a useful tool for investigating inflammatory conditions, prostatic FDG uptake in patients with BPH has not been elucidated. Therefore, we evaluated the association between prostatic FDG uptake and LUTS.METHODSA total of 391 men in their 50s who underwent FDG PET/CT during health examinations were included. Mean and maximal prostatic standard uptake values (SUVs) on FDG PET/CT were measured. Prostatic volume, focal FDG uptake, and calcification were also evaluated. The International Prostate Symptom Score (IPSS) for LUTS was collected at baseline and follow- ups. The correlation between IPSS and other variables was analyzed.RESULTSThe mean age of the study participants was 51.7 years, and the mean follow-up interval was 39.7 months. The average of the mean and maximal SUV for prostatic FDG uptake was 1.8 and 2.6, respectively. The prostate volume was 18.5 cm3. The mean IPSS was 4.82 at baseline and 5.46 at follow-ups. Neither the mean SUV nor the maximal SUV of prostatic FDG uptake was correlated with IPSS at baseline or follow-ups. Conversely, prostate volume was associated with baseline IPSS and follow-up IPSS.CONCLUSIONProstatic FDG uptake did not show a significant association with IPSS on FDG PET/CT as well as at follow-ups. FDG uptake may not reflect prostatic growth in nonmalignant cases

Microporation is a valuable transfection method for efficient gene delivery into human umbilical cord blood-derived mesenchymal stem cells

<p>Abstract</p> <p>Background</p> <p>Mesenchymal stem cells (MSCs) are an attractive source of adult stem cells for therapeutic application in clinical study. Genetic modification of MSCs with beneficial genes makes them more effective for therapeutic use. However, it is difficult to transduce genes into MSCs by common transfection methods, especially nonviral methods. In this study, we applied microporation technology as a novel electroporation technique to introduce enhanced green fluorescent protein (EGFP) and brain-derived neurotropfic factor (BDNF) plasmid DNA into human umbilical cord blood-derived MSCs (hUCB-MSCs) with significant efficiency, and investigated the stem cell potentiality of engineered MSCs through their phenotypes, proliferative capacity, ability to differentiate into multiple lineages, and migration ability towards malignant glioma cells.</p> <p>Results</p> <p>Using microporation with EGFP as a reporter gene, hUCB-MSCs were transfected with higher efficiency (83%) and only minimal cell damage than when conventional liposome-based reagent (<20%) or established electroporation methods were used (30-40%). More importantly, microporation did not affect the immunophenotype of hUCB-MSCs, their proliferation activity, ability to differentiate into mesodermal and ectodermal lineages, or migration ability towards cancer cells. In addition, the BDNF gene could be successfully transfected into hUCB-MSCs, and BDNF expression remained fairly constant for the first 2 weeks <it>in vitro </it>and <it>in vivo</it>. Moreover, microporation of BDNF gene into hUCB-MSCs promoted their <it>in vitro </it>differentiation into neural cells.</p> <p>Conclusion</p> <p>Taken together, the present data demonstrates the value of microporation as an efficient means of transfection of MSCs without changing their multiple properties. Gene delivery by microporation may enhance the feasibility of transgenic stem cell therapy.</p

Serum 25-hydroxyvitamin D levels and risk of colorectal cancer:an age-stratified analysis

Background and aims: the role of circulating 25-hydroxyvitamin D (25(OH)D) in prevention of early-onset colorectal cancer (CRC) in young adults under 50 years is uncertain. We evaluated the age-stratified associations (&lt;50 vs. ≥50 years) :circulating 25(OH)D levels and the risk of CRC in a large sample of Korean adults.Methods: our cohort study included 236,382 participants (mean [standard deviation] age, 38.0 [9.0] years) who underwent a comprehensive health examination, including measurement of serum 25(OH)D levels. Serum 25(OH)D levels were categorized as follows: &lt;10, 10–20, and ≥20 ng/mL. CRC, along with the histologic subtype, site, and invasiveness was ascertained through linkage with the national cancer registry. Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident CRC according to the serum 25(OH)D status, with adjustment for potential confounders.Results: during the 1,393,741 person-years of follow-up (median, 6.5 years; interquartile range, 4.5–7.5 years), 341 participants developed CRC (incidence rate, 19.2 per 105 person-years). Among young individuals aged &lt;50 years, serum 25(OH)D levels were inversely associated with the risk of incident CRC with HRs (95% CIs) of 0.61 (0.43–0.86) and 0.41 (0.27–0.63) for 25(OH)D 10-19 and ≥20 ng/mL, respectively, with respect to the reference (&lt;10 ng/mL) (p for trend &lt;0.001, time-dependent model). Significant associations were evident for adenocarcinoma, colon cancer, and invasive cancers. For those aged ≥50 years, associations were similar, although slightly attenuated compared to younger individuals. Conclusions: serum 25(OH)D levels may have beneficial associations with the risk of developing CRC for both early-onset and late-onset disease. <br/

Association of Polymorphisms in Browzine Journal Cover Fshr, inha, Esr1, and Bmp15 With Recurrent Implantation Failure

Recurrent implantation failure (RIF) refers to two or more unsuccessful in vitro fertilization embryo transfers in the same individual. Embryonic characteristics, immunological factors, and coagulation factors are known to be the causes of RIF. Genetic factors have also been reported to be involved in the occurrence of RIF, and some single nucleotide polymorphisms (SNPs) may contribute to RIF. We examined SNPs i

Delayed Diagnosis of an Intraurethral Foreign Body Causing Urosepsis and Penile Necrosis

Cases of self-inserted foreign bodies in the male urethra and urinary bladder are unusual. In most cases, the type of foreign body can be identified by taking a history or from radiological findings; sometimes, however, it is difficult to identify the foreign body because of decreased mental capacity of the patient or unknown radiological characteristics of the foreign body. We experienced a chronic alcoholic patient with septicemia and penile necrosis in whom a fragment of mirror glass had passed through the urethra into the bladder. The glass, 2 cm in length and 0.7 cm in diameter, was detected by cystoscopy and was removed by using a resectosope

Triplet host engineering for triplet exciton management in phosphorescent organic light-emitting diodes

The device performances of green phosphorescent organic light-emitting diodes with a triplet mixed host emitting layer were correlated with the energy levels and composition of the host materials. Two hole-transport-type host materials, (4,4-N,N -dicarbazole)biphenyl (CBP) and 4,4 ,4 - tris(N-carbazolyl)triphenylamine (TCTA), were combined with two electron-transport-type host materials, 1,3,5-tris(N-phenylbenzimidazole-2-yl)benzene (TPBI) and PH1. The maximum quantum efficiency was obtained in the 5:5 mixed host in the case of TCTA:TPBI and TCTA:PH1, while CBP:PH1 showed the best performances in the 9:1 mixed host. The quantum efficiency of the green mixed host devices was improved by more than 50% compared with that of the corresponding single host devices.Grant No. RTI04-01-02 from the Regional Technology Innovation Program of the Ministry of Commerce, Industry and Energy (MOCIE

Prostate Cancer with Solitary Metastases to the Bilateral Testis

We present the case of an 81-year-old patient with testicular metastasis from prostate carcinoma. After the initial diagnosis of prostate cancer, he had an 8-year course of hormonal therapy and showed no clinical evidence of metastasis to other organs. Asymptomatic metastasis of prostate carcinoma to the testis is a rare clinical condition. We diagnosed his condition, based on histopathology following a subcapsular orchiectomy and transurethral resection of the prostate