Mechanisms of Resistance to Decitabine in the Myelodysplastic Syndrome

Purpose: The DNA methylation inhibitor 5-aza-29-deoxycytidine (DAC) is approved for the treatment of myelodysplastic syndromes (MDS), but resistance to DAC develops during treatment and mechanisms of resistance remain unknown. Therefore, we investigated mechanisms of primary and secondary resistance to DAC in MDS. Patients and Methods: We performed Quantitative Real-Time PCR to examine expression of genes related to DAC metabolism prior to therapy in 32 responders and non-responders with MDS as well as 14 patients who achieved a complete remission and subsequently relapsed while on therapy (secondary resistance). We then performed quantitative methylation analyses by bisulfite pyrosequencing of 10 genes as well as Methylated CpG Island Amplification Microarray (MCAM) analysis of global methylation in secondary resistance. Results: Most genes showed no differences by response, but the CDA/DCK ratio was 3 fold higher in non-responders than responders (P,.05), suggesting that this could be a mechanism of primary resistance. There were no significant differences at relapse in DAC metabolism genes, and no DCK mutations were detected. Global methylation measured by the LINE1 assay was lower at relapse than at diagnosis (P,.05). On average, the methylation of 10 genes was lower at relapse (16.1%) compared to diagnosis (18.1%) (P,.05).MCAM analysis showed decreased methylation of an average of 4.5 % (range 0.6%– 9.7%) of the genes at relapse. By contrast, new cytogenetic changes were found in 20 % of patients

OGX-427 inhibits tumor progression and enhances gemcitabine chemotherapy in pancreatic cancer

Despite many advances in oncology, almost all patients with pancreatic cancer (PC) die of the disease. Molecularly targeted agents are offering hope for their potential role in helping translate the improved activity of combination chemotherapy into improved survival. Heat shock protein 27 (Hsp27) is a chaperone implicated in several pathological processes such as cancer. Further, Hsp27 expression becomes highly upregulated in cancer cells after chemotherapy. Recently, a modified antisense oligonucleotide that is complementary to Hsp27 (OGX-427) has been developed, which inhibits Hsp27 expression and enhances drug efficacy in cancer xenograft models. Phase II clinical trials using OGX-427 in different cancers like breast, ovarian, bladder, prostate and lung are in progress in the United States and Canada. In this study, we demonstrate using TMA of 181 patients that Hsp27 expression and phosphorylation levels increase in moderately differentiated tumors to become uniformly highly expressed in metastatic samples. Using MiaPaCa-2 cells grown both in vitro and xenografted in mice, we demonstrate that OGX-427 inhibits proliferation, induces apoptosis and also enhances gemcitabine chemosensitivity via a mechanism involving the eukaryotic translation initiation factor 4E. Collectively, these findings suggest that the combination of Hsp27 knockdown with OGX-427 and chemotherapeutic agents such as gemcitabine can be a novel strategy to inhibit the progression of pancreas cancer

A low-cost light-weight 3D-printed choke ring for multipath mitigation for GNSS antennas

A low-cost light-weight 3D-printed copper coated choke ring is presented and experimentally demonstrated to have similar performance to a fully metallic choke ring. The conventional metallic choke ring is the standard ground plane used in global navigation satellite systems (GNSS) reference antennas to reject multipath signals. While the choke ring greatly enhances the performance of the antenna, it has the disadvantage of being heavy, bulky, and expensive. One method to reduce the weight and cost of the choke ring, while maintaining the same performance as the metallic structure, is to build the structure using a low-cost, light-weight dielectric material and coating the outside with an electric conductor. In this paper, a prototype of a novel 3D-printed choke ring made from polylactic acid (PLA) plastic and coated with copper tape is fabricated and tested. The novel choke ring is demonstrated to have the same performance as an otherwise heavy and expensive metallic choke ring

Uniform-related infection control practices of dental students

Yazan Aljohani,1 Mohammed Almutadares,1 Khalid Alfaifi,1 Mona El Madhoun,1 Maysoon H Albahiti,2 Nadia Al-Hazmi3 1Internship Program, Faculty of dentistry, King Abdulaziz University, 2Department of Endodontics, King Abdulaziz University, 3Department of Oral Biology, King Abdulaziz University, Faculty of Dentistry, Jeddah, Saudi Arabia Background: Uniform-related infection control practices are sometimes overlooked and underemphasized. In Saudi Arabia, personal protective equipment must meet global standards for infection control, but the country’s Islamic legislature also needs to be taken into account. Aim: To assess uniform-related infection control practices of a group of dental students in a dental school in Saudi Arabia and compare the results with existing literature related to cross-contamination through uniforms in the dental field. Method: A questionnaire was formulated and distributed to dental students at King Abdulaziz University Faculty of Dentistry in Jeddah, Saudi Arabia, which queried the students about their uniform-related infection control practices and their methods and frequency of laundering and sanitizing their uniforms, footwear, and name tags. Results: There is a significant difference between genders with regard to daily uniform habits. The frequency of uniform washing was below the standard and almost 30% of students were not aware of how their uniforms are washed. Added to this, there is no consensus on a unified uniform for male and female students. Conclusion: Information on preventing cross-contamination through wearing uniforms must be supplied, reinforced, and emphasized while taking into consideration the cultural needs of the Saudi society. Keywords: cross-contamination, infection control, dental students, uniform

Millimeter-wave electromagnetic metasurfaces based on perforated dielectrics

A Huygens' unit cell configuration based on perforated dielectrics is proposed and demonstrated using full-wave simulations. The proposed unit cell consists of a high permittivity dielectric resonator surrounded by a honey-comb lattice. The Honey comb structure provides mechanical integrity to the unit cell, thereby enabling the unit cell scaling to mm-wave frequency bands. Two different designs are shown to demonstrate diversity of transmission characteristics achievable through the proposed cells

Multi-Lineage Differentiation of Human Umbilical Cord Wharton’s Jelly Mesenchymal Stromal Cells Mediates Changes in the Expression Profile of Stemness Markers

<div><p>Wharton’s Jelly- derived Mesenchymal stem cells (WJ-MSCs) have gained interest as an alternative source of stem cells for regenerative medicine because of their potential for self-renewal, differentiation and unique immunomodulatory properties. Although many studies have characterized various WJ-MSCs biologically, the expression profiles of the commonly used stemness markers have not yet been addressed. In this study, WJ-MSCs were isolated and characterized for stemness and surface markers expression. Flow cytometry, immunofluorescence and qRT-PCR analysis revealed predominant expression of CD29, CD44, CD73, CD90, CD105 and CD166 in WJ-MSCs, while the hematopoietic and endothelial markers were absent. Differential expression of CD 29, CD90, CD105 and CD166 following adipogenic, osteogenic and chondrogenic induction was observed. Furthermore, our results demonstrated a reduction in CD44 and CD73 expressions in response to the tri-lineage differentiation induction, suggesting that they can be used as reliable stemness markers, since their expression was associated with undifferentiated WJ-MSCs only.</p></div