8 research outputs found
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Delivery of Functional Anti-miR-9 by Mesenchymal Stem Cell–derived Exosomes to Glioblastoma Multiforme Cells Conferred Chemosensitivity
Glioblastoma multiforme (GBM), the most common and lethal tumor of the adult brain, generally shows chemo- and radioresistance. MicroRNAs (miRs) regulate physiological processes, such as resistance of GBM cells to temozolomide (TMZ). Although miRs are attractive targets for cancer therapeutics, the effectiveness of this approach requires targeted delivery. Mesenchymal stem cells (MSCs) can migrate to the sites of cancers, including GBM. We report on an increase in miR-9 in TMZ-resistant GBM cells. miR-9 was involved in the expression of the drug efflux transporter, P-glycoprotein. To block miR-9, methods were developed with Cy5-tagged anti-miR-9. Dye-transfer studies indicated intracellular communication between GBM cells and MSCs. This occurred by gap junctional intercellular communication and the release of microvesicles. In both cases, anti-miR-9 was transferred from MSCs to GBM cells. However, the major form of transfer occurred with the microvesicles. The delivery of anti-miR-9 to the resistant GBM cells reversed the expression of the multidrug transporter and sensitized the GBM cells to TMZ, as shown by increased cell death and caspase activity. The data showed a potential role for MSCs in the functional delivery of synthetic anti-miR-9 to reverse the chemoresistance of GBM cells
Second Trimester Cervical Ectopic Pregnancy and Hemorrhage: A Case Report and Review of the Literature
Cervical ectopic pregnancies are a rare occurrence in the United States. Here we present the interdisciplinary and conservative management approach to a cervical ectopic at an advanced gestational age. In addition, we review the surgical management of hemorrhage from cervical ectopic pregnancies, which is often catastrophic and life-threatening
Mycoplasma genitalium: An Emerging Sexually Transmitted Infection
Mycoplasma genitalium has been recognized as a cause of male urethritis, and there is now evidence suggesting that it causes cervicitis and pelvic inflammatory disease in women. M. genitalium is a slow growing organism, and, with the advent of nucleic acid amplification test (NAAT), more studies are being performed, and knowledge about the pathogenicity of this organism elucidated. With NAAT detection, treatment modalities have been studied, and the next challenge is to determine the most effective antimicrobial therapy. Doxycycline, the first-line antibiotic for urethritis, is largely ineffective in the treatment of M. genitalium and furthermore, resistance to macrolide has also emerged. The most effective drug is Moxifloxacin although there are emerging reports of resistance to it in various parts of the world. This paper not only highlights the current research and knowledge, but also reviews the diversity of health implications on the health of men and women infected with M. genitalium. Alternate antibiotics and the impact of M. genitalium on infertility are areas that require more studies as we continue to research into this microorganism
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Temozolomide resistance in glioblastoma occurs by miRNA-9-targeted PTCH1, independent of sonic hedgehog level
Glioblastoma Multiforme (GBM), the most common and lethal adult primary tumor of the brain, showed a link between Sonic Hedgehog (SHH) pathway in the resistance to temozolomide (TMZ). PTCH1, the SHH receptor, can tonically represses signaling by endocytosis. We asked how the decrease in PTCH1 in GBM cells could lead to TMZ-resistance. TMZ resistant GBM cells have increased PTCH1 mRNA and reduced protein. Knockdown of Dicer, a Type III RNAase, indicated that miRNAs can explain the decreased PTCH1 in TMZ resistant cells. Computational studies, real-time PCR, reporter gene studies, western blots, target protector oligos and ectopic expression identified miR-9 as the target of PTCH1 in resistant GBM cells with concomitant activation of SHH signaling. MiR-9 mediated increases in the drug efflux transporters, MDR1 and ABCG2. MiR-9 was increased in the tissues from GBM patients and in an early passage GBM cell line from a patient with recurrent GBM but not from a naïve patient. Pharmacological inhibition of SHH signaling sensitized the GBM cells to TMZ. Taken together, miR-9 targets PTCH1 in GBM cells by a SHH-independent method in GBM cells for TMZ resistance. The identified pathways could lead to new strategies to target GBM with combinations of drugs