Flow-induced Shear Stress Confers Resistance to Carboplatin in an Adherent Three-Dimensional Model for Ovarian Cancer: A Role for EGFR-Targeted Photoimmunotherapy Informed by Physical Stress.

A key reason for the persistently grim statistics associated with metastatic ovarian cancer is resistance to conventional agents, including platinum-based chemotherapies. A major source of treatment failure is the high degree of genetic and molecular heterogeneity, which results from significant underlying genomic instability, as well as stromal and physical cues in the microenvironment. Ovarian cancer commonly disseminates via transcoelomic routes to distant sites, which is associated with the frequent production of malignant ascites, as well as the poorest prognosis.

Marital Status and Overall Survival in Patients with Resectable Pancreatic Cancer: Results of an Ancillary Analysis of NRG Oncology/RTOG 9704.

Background: Several registry-based analyses suggested a survival advantage for married versus single patients with pancreatic cancer. The mechanisms underlying the association of marital status and survival are likely multiple and complex and, therefore, may be obscured in analyses generated from large population-based databases. The goal of this research was to characterize this potential association of marital status with outcomes in patients with resected pancreatic cancer who underwent combined modality adjuvant therapy on a prospective clinical trial.

Retraction Note to: Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression.

The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figures 1B and 1D, the cell lines are different and all published histograms show SEMA4D mRNA level whereas Excel data have two histograms showing SEMA4D expression and two histograms showing VEGF expression. In Figure 2B, the metadata for one image shows different treatment conditions than those reported in the article.

Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy.

The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue.

Novel Bioactive and Therapeutic Root Canal Sealers with Antibacterial and Remineralization Properties.

According to the American Dental Association Survey of Dental Services Rendered (published in 2007), 15 million root canal treatment procedures are performed annually. Endodontic therapy relies mainly on biomechanical preparation, chemical irrigation and intracanal medicaments which play an important role in eliminating bacteria in the root canal. Furthermore, adequate obturation is essential to confine any residual bacteria within the root canal and deprive them of nutrients.

Retraction Note to: The Semaphorin 4D-Plexin-B1-RhoA signaling axis recruits pericytes and regulates vascular permeability through endothelial production of PDGF-B and ANGPTL4.

The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figure 1C, the graph showing PDGF-B does not match the original data for the 24-hour time point. The graph shows the value to be over 1000 pg/ml, but the original data have a value of 106.

Correction to: Rho-mediated activation of PI(4)P5K and lipid second messengers is necessary for promotion of angiogenesis by Semaphorin 4D.

Figure 3c of this article originally contained standard deviation values which had not been calculated correctly. A single standard deviation value was used for all 5 time points for each condition.

Weighty choices: selecting optimal G-CSF doses for stem cell mobilization to optimize yield.

There are limited data on the effect of donor body mass index (BMI) on peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF), especially in unrelated donors. Obesity has been associated with persistent leukocytosis, elevated circulating progenitor cells, and enhanced stem cell mobilization. Therefore, we hypothesized that adequate collection of CD34+ cells may be achieved with lower doses (per kilogram of body weight) of G-CSF in donors with higher BMI compared with donors with lower BMI.

Histone Demethylase JMJD1A Promotes Tumor Progression via Activating Snail in Prostate Cancer.

The histone demethylase JMJD1A plays a key functional role in spermatogenesis, sex determination, stem cell renewal, and cancer via removing mono- and di-methyl groups from H3K9 to epigenetically control gene expression. However, its role in prostate cancer progression remains unclear. Here, we found JMJD1A was significantly elevated in prostate cancer tissue compared with matched normal tissue.

Phage display as a tool for vaccine and immunotherapy development.

Bacteriophages, or phages, are viruses that specifically infect bacteria and coopt the cellular machinery to create more phage proteins, eventually resulting in the release of new phage particles. Phages are heavily utilized in bioengineering for applications ranging from tissue engineering scaffolds to immune signal delivery. Of specific interest to vaccines and immunotherapies, phages have demonstrated an ability to activate both the innate and adaptive immune systems.

Results of the NRG Oncology/RTOG 0848 Adjuvant Chemotherapy Question-Erlotinib+Gemcitabine for Resected Cancer of the Pancreatic Head: A Phase II Randomized Clinical Trial.

Purpose: NRG/RTOG 0848 was designed to determine whether adjuvant radiation with fluoropyrimidine sensitization improved survival following gemcitabine-based adjuvant chemotherapy for patients with resected pancreatic head adenocarcinoma. In step 1 of this protocol, patients were randomized to adjuvant gemcitabine versus the combination of gemcitabine and erlotinib. This manuscript reports the final analysis of these step 1 data.

Immunological and Toxicological Considerations for the Design of Liposomes.

Liposomes hold great potential as gene and drug delivery vehicles due to their biocompatibility and modular properties, coupled with the major advantage of attenuating the risk of systemic toxicity from the encapsulated therapeutic agent. Decades of research have been dedicated to studying and optimizing liposomal formulations for a variety of medical applications, ranging from cancer therapeutics to analgesics. Some effort has also been made to elucidate the toxicities and immune responses that these drug formulations may elicit.

Radiation dose-painting with protons vs. photons for head-and-neck cancer.

Dose-painting has recently been investigated in early-phase trials in head-and-neck cancer (HNC) with the aim of improving local tumor control. At the same time proton therapy has been reported as potentially capable of decreasing toxicity. Here, we investigate whether protons could be applied in a dose-painting setting by comparing proton dose distributions with delivered photon plans from a phase-I trial of FDG-PET based dose-painting at our institution.

S. mutans gene-modification and antibacterial resin composite as dual strategy to suppress biofilm acid production and inhibit caries.

Objective: Composite restorations are increasingly popular, but recurrent caries is a main reason for composite restoration failures. The objectives of this study were to investigate a dual strategy of combining rnc gene-deletion for Streptococcus mutans (S. mutans) with antibacterial dimethylaminohexadecyl methacrylate (DMAHDM) composite, and determine the effects of rnc gene-deletion alone, DMAHDM composite alone, and rnc-deletion plus DMAHDM composite, on biofilm growth and lactic acid production.

Breaking the selectivity-uptake trade-off of photoimmunoconjugates with nanoliposomal irinotecan for synergistic multi-tier cancer targeting.

Background: Photoimmunotherapy involves targeted delivery of photosensitizers via an antibody conjugate (i.e., photoimmunoconjugate, PIC) followed by light activation for selective tumor killing.

Photodynamic Therapy and the Biophysics of the Tumor Microenvironment.

Targeting the tumor microenvironment (TME) provides opportunities to modulate tumor physiology, enhance the delivery of therapeutic agents, impact immune response and overcome resistance. Photodynamic therapy (PDT) is a photochemistry-based, nonthermal modality that produces reactive molecular species at the site of light activation and is in the clinic for nononcologic and oncologic applications. The unique mechanisms and exquisite spatiotemporal control inherent to PDT enable selective modulation or destruction of the TME and cancer cells.

Harnessing the Potential Synergistic Interplay Between Photosensitizer Dark Toxicity and Chemotherapy.

The combination of photodynamic therapy and taxol- or platinum-based chemotherapy (photochemotherapy) is an effective and promising cancer treatment. While the mechanisms of action of photochemotherapy are actively studied, relatively little is known about the cytotoxicity and molecular alterations induced by the combination of chemotherapy and photosensitizers without light activation in cancer cells. This study investigates the interplay between the photosensitizer benzoporphyrin derivative (BPD) without light activation and cisplatin or paclitaxel in two glioblastoma lines, U87 and U251.

Cost effective, experimentally robust differential-expression analysis for human/mammalian, pathogen and dual-species transcriptomics.

As sequencing read length has increased, researchers have quickly adopted longer reads for their experiments. Here, we examine 14 pathogen or host-pathogen differential gene expression data sets to assess whether using longer reads is warranted. A variety of data sets was used to assess what genomic attributes might affect the outcome of differential gene expression analysis including: gene density, operons, gene length, number of introns/exons and intron length.

Effects of gene-modification and antibacterial calcium phosphate nanocomposite on secondary caries and marginal enamel hardness.

Secondary caries at the restoration-tooth margins is a main reason for dental restoration failures. Gene-modification for () and composites containing dimethylaminohexadecyl methacrylate (DMAHDMA) and nanoparticles of amorphous calcium phosphate (NACP) all have the potential to suppress bacterial acids and promote remineralization. However, there has been no report of their effects on marginal caries-inhibition and enamel hardness.

Human periodontal ligament stem cells on calcium phosphate scaffold delivering platelet lysate to enhance bone regeneration.

Human periodontal ligament stem cells (hPDLSCs) are promising for tissue engineering applications but have received relatively little attention. Human platelet lysate (HPL) contains a cocktail of growth factors. To date, there has been no report on hPDLSC seeding on scaffolds loaded with HPL.

Stem cells in the periodontal ligament differentiated into osteogenic, fibrogenic and cementogenic lineages for the regeneration of the periodontal complex.

Objective: Human periodontal ligament stem cells (hPDLSCs) are promising for periodontal regeneration. However, to date, there has been no report of hPDLSC differentiation into the fibrogenic lineage. There has been no report demonstrating hPDLSC differentiation into all three (osteogenic, fibrogenic and cementogenic fibrogenic) lineages in the same report.

Drug Repurposing of Bromodomain Inhibitors as Potential Novel Therapeutic Leads for Lymphatic Filariasis Guided by Multispecies Transcriptomics.

To better understand the transcriptomic interplay of organisms associated with lymphatic filariasis, we conducted multispecies transcriptome sequencing (RNA-Seq) on the filarial nematode , its endosymbiont Bm, and its laboratory vector across the entire life cycle. In Bm, transcription of the noncoding 6S RNA suggests that it may be a regulator of bacterial cell growth, as its transcript levels correlate with bacterial replication rates. For , the transcriptional response reflects the stress that infection exerts on the mosquito with indicators of increased energy demand.