Preparation of polylactide-co-glycolide nanoparticles incorporating celecoxib and their antitumor activity against brain tumor cells

Tae-Ho Kim1*, Young-Il Jeong2*, Shu-Guang Jin2, Jian Pei2, Tae-Young Jung1, Kyung-Sub Moon1, In-Young Kim1, Sam-Suk Kang1, Shin Jung1,21Department of Neurosurgery, 2Brain Tumor Research Laboratory, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, Gwangju, Republic of Korea *These authors contributed equally to this work. Background: Celecoxib, a cyclo-oxygenase (COX)-2 inhibitor, has been reported to mediate growth inhibitory effects and to induce apoptosis in various cancer cell lines. In this study, we examined the potential effects of celecoxib on glioma cell proliferation, migration, and inhibition of COX-2 expression in vitro. Methods: Celecoxib was incorporated into poly DL-lactide-co-glycolide (PLGA) nanoparticles for antitumor drug delivery. Results: PLGA nanoparticles incorporating celecoxib had spherical shapes and their particle sizes were in the range of 50–200 nm. Drug-loading efficiency was not significantly changed according to the solvent used, except for acetone. Celecoxib was released from the PLGA nanoparticles for more than 2 days, and the higher the drug content, the longer the duration of drug release. PLGA nanoparticles incorporating celecoxib showed cytotoxicity against U87MG tumor cells similar to that of celecoxib administered alone. Furthermore, celecoxib did not affect the degree of migration of U87MG cells. PLGA nanoparticles incorporating celecoxib showed dose-dependent cytotoxicity similar to that of celecoxib alone in C6 rat glioma cells. Western blot assay of the C6 cells showed that neither celecoxib alone nor PLGA nanoparticles incorporating celecoxib affected COX-2 expression. Conclusion: PLGA nanoparticles incorporating celecoxib had antitumor activity similar to that of celecoxib alone, even though these particles did not affect the degree of migration or COX-2 expression in the tumor cells. Keywords: celecoxib, cyclo-oxygenase-2, PLGA nanoparticles, glioma, antitumor activit

Do corporate governance and culture matter in cross-border acquisitions? Some Chinese evidence

The Chinese market for corporate control has recently gained much academic attention. This research constructs a sample of 159 cross-border acquisitions made by 123 Chinese firms between 2010 and 2014 and relates the roles of governance and culture to the wealth effects of mergers. First, the shareholders of Chinese bidders experience gains upon the announcement of overseas mergers. Second, country- and firm-level governance notably affects the cumulative abnormal returns of Chinese acquirers. Lastly, and however, the cultural distance per Hofstede’s (1980) four cultural dimensions does not appear to be a significant factor in determining the shareholder wealth of Chinese purchasers

A Spinal Cord Astrocytoma and Its Concurrent Osteoblastic Metastases at the Time of the Initial Diagnosis: a Case Report and Literature Review

Bone metastasis from a spinal cord astrocytoma has been reported only twice in the English medical literature. It is generally known that bone metastasis is found after the initial diagnosis with/without intervening surgery rather than being found at the time of the diagnosis of astrocytoma. The purpose of this article is to report for the first time a case of concurrent bone metastasis from a spinal cord astrocytoma at the time of diagnosing the spinal cord astrocytoma

Left anterior descending artery dissection with retrograde aortic dissection during percutaneous coronary intervention: a case report

Retrograde catheter-induced coronary artery dissection during percutaneous coronary intervention is an exceedingly rare occurrence, and the likelihood of it extending into the aorta is even more uncommon. Typically, surgical treatment involves aortic root replacement combined with coronary artery bypass grafting. However, in this particular case, a meticulous approach was employed. By carefully guiding wires into the true lumens and placing stents in the proximal left main and left anterior descending arteries, the immediate complications were averted by obstructing the retrograde flow in the false lumen. Subsequently, an off-pump coronary artery bypass was performed using the left internal mammary artery to the left anterior descending artery, without the need to manipulate the aorta. This approach resulted in a short operation time and the absence of any other complications

The Surgical Outcome of Endoscopic Dacryocystorhinostomy According to the Obstruction Levels of Lacrimal Drainage System

ObjectivesMany factors influence the outcome of endoscopic dacryocystorhinostomy (DCR). One of the most important prognostic factors is the level of obstruction in the lacrimal drainage system. The main objective of this report is to evaluate both the frequency of obstruction by anatomical region of the lacrimal drainage system on dacryocystography (DCG) and the surgical outcome of endoscopic DCR according to the obstruction level.MethodsA retrospective series of 48 patients (60 eyes) who had undergone endoscopic DCR from January 2005 to November 2007 were enrolled. Preoperative evaluation consisted of a standard examination which included lacrimal irrigation, probing, DCG and osteomeatal unit (OMU) computed tomography. Patients were classified into four groups according to the obstruction level on DCG. Surgical outcome was evaluated postoperatively by subjective improvement of epiphora and patent rhinostomy opening on nasal endoscopic exam.ResultsOf 60 eyes, the levels of obstruction were the common canaliculus in 14 eyes (23.3%), the lacrimal sac in 13 eyes (21.7%), the duct-sac junction in 13 eyes (21.7%) and the nasolacrimal duct (NLD) in 20 eyes (33.3%). The ductsac junction obstruction was treated most successfully (100%), followed by NLD obstruction (90%), common canaliculus obstruction (78.6%) and saccal obstruction (69.2%).ConclusionIn patients with lacrimal drainage system obstruction, preoperative evaluation of obstruction level using DCG may be helpful for predicting the surgical outcome of endoscopic DCR. The saccal obstruction may have a worse prognosis than the other obstruction levels

Metastatic Glioblastoma in Cervical Lymph Node after Repeated Craniotomies: Report of a Case with Diagnosis by Fine Needle Aspiration

Head and neck metastasis from glioblastoma is rare event usually seen in patients with previous and repeated surgery. We present the case of a 35 yr-old-female suffering from metastatic glioblastoma in cervical lymph node that was diagnosed by fine needle aspiration. During the last 4 yr, she had four separate craniotomies for the recurrent brain tumors. Cytological diagnosis was made by light microscopy with immunostaining with glial fibrillay acid protein. Chemotherapy with vincristine and procarbazine was performed. The cervical masses were decreased in size and some disappeared while the intracranial glioblastoma continued to grow during chemotherapy. We discuss possible explanations for these different courses after chemotherapy in extraneural metastatic glioblastoma and primary intracranial glioblastoma

Melatonin receptor 1 B polymorphisms associated with the risk of gestational diabetes mellitus

<p>Abstract</p> <p>Backgrounds</p> <p>Two SNPs in <it>melatonin receptor 1B </it>gene, <it>rs10830963 </it>and <it>rs1387153 </it>showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM) in previous studies. Since T2DM and gestational diabetes mellitus (GDM) share similar characteristics, we suspected that the two genetic polymorphisms in <it>MTNR1B </it>may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes.</p> <p>Methods</p> <p>A total of 1,918 subjects (928 GDM patients and 990 controls) were used for the study. Two <it>MTNR1B </it>polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by <it>x</it>²models calculating odds ratios (ORs), 95% confidence intervals (CIs), and corresponding <it>P </it>values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed.</p> <p>Results</p> <p>We found significant associations between the two genetic variants and GDM, <it>rs10830963</it>, with a corrected <it>P </it>value of 0.0001, and <it>rs1387153</it>, with the corrected <it>P </it>value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that <it>rs10830963 </it>might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses.</p> <p>Conclusion</p> <p>There have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of <it>MTNR1B </it>and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.</p

A Case of Asymptomatic Multiple Endocrine Neoplasia Type I with Thymic Carcinoid

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder caused by germline mutation of the MEN1 gene. It is characterized by tumors of the anterior pituitary gland, parathyroid glands, and endocrine pancreas. Thymic carcinoid tumor is uncommon and associated with a high mortality, but its natural history has not been investigated yet. We report a case of asymptomatic MEN 1 with a thymic carcinoid tumor. A 37-year-old man underwent a routine medical checkup and upper gastrointestinal endoscopy revealed a duodenal neuroendocrine tumor (NET). Further studies showed the coexistence of pancreatic tumor, parathyroid hyperplasia, pituitary adenoma, and thymoma. The patient underwent duodenal endoscopic mucosal resection, distal pancreatectomy, subtotal parathyroidectomy, and thymectomy. The pathological test revealed a duodenal NET, pancreatic NET, parathyroid hyperplasia, and thymic carcinoid tumor. He was treated for MEN 1. We report this asymptomatic case of MEN 1 with a literature review

Limited Effect of CpG ODN in Preventing Type 1 Diabetes in NOD Mice

Type 1 diabetes is considered as Th1 cell mediated autoimmune disease and the suppression of Th1 cells or the activation of Th2 cells has been regarded as a plausible immunologic intervention for the prevention of type 1 diabetogenesis in a rodent model. CpG ODN is an immunostimulatory sequence primarily present in bacterial DNA, viral DNA and BCG. CpG ODN is conventionally classified as a Th1 cell activator, which has been clinically applied to cancer, allergy and infectious disease. Recently, there was a promising report of that CpG ODN administration suppressed the development of type 1 diabetes in NOD mice by inducing Th2 cell mediated cytokine. However, the antidiabetogenic effect of CpG ODN on NOD mice is controversial. Thus, two studies were serially undertaken with various kinds of CpG motif to find a more optimal sequence and administration method. In the first study, CpG ODN was vaccinated four times and pancreatic inflammation and the quantity of serum insulin subsequently evaluated. In the second study, the amounts of IFN γ and IL-4 in sera were measured as representative cytokines of Th1 and Th2 cells, respectively. As a result, vaccination or continuous injection of CpG ODN failed to show a preventive effect on type 1 diabetogenesis in NOD mice. Structural differences of CpG ODN also had no affect on the result. CpG ODN also consistently showed affect on the pancreatic pathology. The productions of IFN and IL-4 were γ detected only in the K and D type CpG ODN administration groups. Comparison of the two cytokines leads to the conclusion that CpG ODN generated a Th1-weighted response in both study groups. It was assumed that CpG ODN failed to produce Th2-weighted cytokine milieu, which can overcome the genetically determined phenotype of NOD mice. Given these results, it was concluded that the immunotherapeutic application of CpG ODN on Type 1 diabetes had clear limitations

Intracranial metastasis from primary transitional cell carcinoma of female urethra: case report & review of the literature

<p>Abstract</p> <p>Background</p> <p>Transitional cell carcinoma (TCC) of the female urethra is a rare urological malignancy, and intracranial metastasis of this cancer has not yet been reported in the literature. This review is intended to present a case of multiple intracranial metastasis in a female patient with a remote history of primary urethral TCC.</p> <p>Case Presentation</p> <p>A 49-year-old woman, presented with a prolapsed mass in urethral orifice that was diagnosed as primary urethral TCC with distant lung and multiple bone metastases. The patient subsequently underwent chemotherapy under various regimens. A year later, the patient developed headache and vomiting which as was found to be due to multiple intracranial metastasis. The patient underwent surgical resection of the largest lesion located on the cerebellum, and consecutively gamma knife radiosurgery was performed for other small-sized lesions. Pathological examination of the resected mass revealed a metastatic carcinoma from a known urethral TCC. Serial work-up of systemic metastasis revealed concomitant aggravation of lung, spleen, and liver metastasis. The patient died of lung complication 2 months after the diagnosis of brain metastasis.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first reported case of cerebral metastasis from primary urethral TCC, with pathological confirmation. As shown in intracranial metastasis of other urinary tract carcinoma, this case occurred in the setting of uncontrolled systemic disease and led to dismal prognosis in spite of aggressive interventional modalities.</p