The effects of kainic acid on the cochlear ganglion of the rat

The effects of locally applied kainic acid on cells and fibers in the rat cochlea were examined in a quantitative and ultrastructural study. Doses of 5 nM per [mu]1 of artificial perilymph destroyed part of the spiral ganglion type I cell population, with no ototoxic effects on cochlear hair cells or supporting cells. Type II cells also appeared unaffected. A quantitative evaluation of the cell loss with the 5 nM dosage showed that 34% of spiral ganglion neurons were lost 10 days after treatment. Doses of 20 nM per [mu]l and 40 nM per [mu]1 did not result in increasing neuronal loss.This differential toxicity could reflect the presence of a sub-population of spiral ganglion cells with an increased number of KA receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27881/1/0000295.pd

Trends of maxillofacial trauma : an update from the prospective register of a multicenter study in emergency services of Chile

Determine the behavior of the maxillofacial trauma of adults treated in 3 tertiary care centers in the central zone of Chile. Descriptive, cross-sectional, multicenter study, based on the prospective records of maxillofacial trauma cases attended between May 2016 and April 2017 by dental and maxillofacial clinical teams of Adult Emergency Units of hospitals Dr. Sótero del Río (metropolitan region), Carlos Van Buren and Dr. Gustavo Fricke (region V). Age, sex, date of occurrence, type of trauma according to ICD-10, etiology, legal medical prognosis and associated injuries were recorded, stratifying by sex and age. Chi square and unpaired Wilcoxon tests were used to compare by groups. 2.485 cases and 3.285 injuries were investigated. The male: female ratio was 1.7: 1 with age under 30 predominant, followed by older adults. Variability was observed in the yearly, weekly and daily presentation. The highest frequencies were in January and September, weekends and at night. The main etiologies were violence (42.3%), falls (13.1%) and road traffic crashes (12.9%) with differences by age and sex (p<0.05). 31,9% of the injuries occurred in hard tissue, being fractures in nasal bones predominant (S02.2). The profile of the maxillofacial trauma in Chile seems to be mixed by age, affecting young people and the elderly. The male sex predominates; the main cause, which varies by age group, is violence. Their surveillance is possible from hospital emergency records

Antiangiogenic Activity of 2-Deoxy-D-Glucose

During tumor angiogenesis, endothelial cells (ECs) are engaged in a number of energy consuming biological processes, such as proliferation, migration, and capillary formation. Since glucose uptake and metabolism are increased to meet this energy need, the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on in vitro and in vivo angiogenesis were investigated.In cell culture, 2-DG inhibited EC growth, induced cytotoxicity, blocked migration, and inhibited actively forming but not established endothelial capillaries. Surprisingly, 2-DG was a better inhibitor of these EC properties than two more efficacious glycolytic inhibitors, 2-fluorodeoxy-D-glucose and oxamate. As an alternative to a glycolytic inhibitory mechanism, we considered 2-DG's ability to interfere with endothelial N-linked glycosylation. 2-DG's effects were reversed by mannose, an N-linked glycosylation precursor, and at relevant concentrations 2-DG also inhibited synthesis of the lipid linked oligosaccharide (LLO) N-glycosylation donor in a mannose-reversible manner. Inhibition of LLO synthesis activated the unfolded protein response (UPR), which resulted in induction of GADD153/CHOP and EC apoptosis (TUNEL assay). Thus, 2-DG's effects on ECs appeared primarily due to inhibition of LLOs synthesis, not glycolysis. 2-DG was then evaluated in two mouse models, inhibiting angiogenesis in both the matrigel plug assay and the LH(BETA)T(AG) transgenic retinoblastoma model.In conclusion, 2-DG inhibits endothelial cell angiogenesis in vitro and in vivo, at concentrations below those affecting tumor cells directly, most likely by interfering with N-linked glycosylation rather than glycolysis. Our data underscore the importance of glucose metabolism on neovascularization, and demonstrate a novel approach for anti-angiogenic strategies

A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma

BACKGROUND: 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) is superior to gemcitabine in patients with metastatic pancreatic cancer who have a good performance status. We investigated this combination as neoadjuvant therapy for locally advanced pancreatic cancer (LAPC). METHODS: In this retrospective series, we included patients with unresectable LAPC who received neoadjuvant FOLFIRINOX with growth factor support. The primary analysis endpoint was R0 resection rate. RESULTS: Eighteen treatment-naïve patients with unresectable or borderline resectable LAPC were treated with neoadjuvant FOLFIRINOX. The median age was 57.5 years and all had ECOG PS of 0 or 1. Eleven (61 %) had tumors in the head of the pancreas and 9 (50 %) had biliary stents placed prior to chemotherapy. A total of 146 cycles were administered with a median of 8 cycles (range 3-17) per patient. At maximum response or tolerability, 7 (39 %) were converted to resectability by radiological criteria; 5 had R0 resections, 1 had an R1 resection, and 1 had unresectable disease. Among the 11 patients who remained unresectable after FOLFIRINOX, 3 went on to have R0 resections after combined chemoradiotherapy, giving an overall R0 resection rate of 44 % (95 % CI 22–69 %). After a median follow-up of 13.4 months, the 1-year progression-free survival was 83 % (95 % CI 59-96 %) and the 1-year overall survival was 100 % (95 % CI 85-100 %). Grade 3/4 chemotherapy-related toxicities were neutropenia (22 %), neutropenic fever (17 %), thrombocytopenia (11 %), fatigue (11 %), and diarrhea (11 %). Common grade 1/2 toxicities were neutropenia (33 %), anemia (72 %), thrombocytopenia (44 %), fatigue (78 %), nausea (50 %), diarrhea (33 %) and neuropathy (33 %). CONCLUSIONS: FOLFIRINOX followed by chemoradiotherapy is feasible as neoadjuvant therapy in patients with unresectable LAPC. The R0 resection rate of 44 % in this population is promising. Further studies are warranted

Formation guide in industry 4.0

La cuanta revolución industrial está en pleno auge y en países como el nuestro el desarrollo e implementación de la tecnología no es un punto fuerte, es por eso que en este trabajo se presentan las tecnologías que hacen parte de la industria 4.0, utilizando distintas fuentes bibliográficas con el fin de que los lectores se familiaricen con la temática del cambio tecnológico que se está viviendo el mundo y como esto se adapta a los procesos cotidianos y productivos en diferentes niveles y escenarios.The fourth industrial revolution is booming and in countries like ours the development and implementation of technology is not a strong point, that is why this work presents the technologies that are part of Industry 4.0, using different sources in order for readers to become familiar with the theme of technological change that the world is experiencing and how this adapts to everyday and productive processes at different levels and scenarios

Immunotherapy in Renal Cell Carcinoma

Renal cell carcinoma (RCC) is a chemotherapy-resistant disease, and current molecularly targeted therapies offer limited clinical benefit but no cures. The observation that RCC is immunogenic led to immune-based strategies for the treatment of this disease. Immunotherapy with high-dose IL-2 can induce long-term, complete responses in a small percentage of patients. IFN has been used as an immune intervention as well but with much less success than IL-2. Currently IFN is used only in combination with the anti-VEGF monoclonal antibody bevacizumab. Further investigation of novel immune interventions in RCC is ongoing with promising results. Dendritic cell vaccines have been tested in single-arm clinical trials suggesting improved survival when added to standard anti-angiogenic therapy. Monoclonal antibodies against PD-1 and PD-L1, novel immune targets, have shown promising response in phase I trials. Peptide vaccines have shown efficacy in phase II trials as well. Phase III trials to test these immune interventions are currently ongoing and have the potential to bring new, effective treatment options for patients with advanced RCC

Targeting tumor vasculature through oncolytic virotherapy: recent advances

The oncolytic virotherapy field has made significant advances in the last decade, with a rapidly increasing number of early- and late-stage clinical trials, some of them showing safety and promising therapeutic efficacy. Targeting tumor vasculature by oncolytic viruses (OVs) is an attractive strategy that offers several advantages over nontargeted viruses, including improved tumor viral entry, direct antivascular effects, and enhanced antitumor efficacy. Current understanding of the biological mechanisms of tumor neovascularization, novel vascular targets, and mechanisms of resistance has allowed the development of oncolytic viral vectors designed to target tumor neovessels. While some OVs (such as vaccinia and vesicular stomatitis virus) can intrinsically target tumor vasculature and induce vascular disruption, the majority of reported vascular-targeted viruses are the result of genetic manipulation of their viral genomes. Such strategies include transcriptional or transductional endothelial targeting, “armed” viruses able to downregulate angiogenic factors, or to express antiangiogenic molecules. The above strategies have shown preclinical safety and improved antitumor efficacy, either alone, or in combination with standard or targeted agents. This review focuses on the recent efforts toward the development of vascular-targeted OVs for cancer treatment and provides a translational/clinical perspective into the future development of new generation biological agents for human cancers

Abstract 3745: Tumor fibroblast targeting via uPAR retargeted measles virus: In vitro and in vivo effects

Tumor stromal cell components, in particular cancer associated fibroblasts, play an important role in cancer progression. Few studies have focused on stromal fibroblast targeting by oncolytic viruses. The urokinase receptor (uPAR) is a clinically and biologically validated target, which is overexpressed in tumor and stromal cells compared to non-cancer tissues. MV-h-uPA and MV-m-uPA are fully retargeted oncolytic measles viruses directed against human and murine uPAR, respectively, which have shown in vitro and in vivo safety and antitumor effects. Species specific retargeted viral vectors allow to dissect the specific effects of the viruses on murine vs. human tissues in xenograft models. Our aim is to characterize the in vitro and in vivo effects of stromal targeting by oncolytic measles virus via uPAR, with a focus on tumor fibroblasts. In vitro, MV-h-uPA and MV-m-uPA preferentially infected and induced cytotoxicity in human cancer associated fibroblasts (CAF 19, CAF 23) as well as murine fibroblasts (3T3), compared to non-tumorigenic fibroblasts. Murine-murine and human-human fibroblast to cancer cell viral transfer via heterofusion was observed after fibroblast infection by species specific MV-uPA, in breast, colon and renal cancer models, while no viral transfer was observed between cells of different species. In vivo, systemic administration of the murine uPA retargeted virus (MV-m-uPA) significantly decreased tumor progression and prolonged survival in a human breast cancer xenograft model (MDA-MD231), where the host stroma expresses murine uPAR (target of MV-m-uPA). Tumor studies revealed induction of apoptosis (TUNEL assay), while no significant effects on cancer cell proliferation was observed. Dual staining for measles virus nucleocapsid proteins and fibroblasts markers demonstrated viral infection of fibroblasts in treated tumors. Gene expression studies using murine as well as human specific arrays were performed to characterize the effects of stromal targeting by the murine retargeted virus on murine stroma as well as the indirect effects on human cancer cells in vivo