Impact of rhG-CSF on Clinical Efficacy and Immune Cell Subsets after Initial Induction Chemotherapy in AML.

Background: The impact of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in acute myeloid leukemia (AML) is still controversial. The purpose of this study is to explore the impact of rhG-CSF administration on clinical efficacy and immune cell subsets after initial induction chemotherapy in AML.

Methods: The clinical efficacy and immune cell subsets were compared in the newly diagnosed patients with AML according to whether rhG-CSF was used after initial induction chemotherapy.

Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies.

Pancreatic ductal adenocarcinoma (PDAC) exhibits a variety of phenotypes with regard to disease progression and treatment response. This variability complicates clinical decision-making despite the improvement of survival due to the recent introduction of FOLFIRINOX (FFX) and nab-paclitaxel. Questions remain as to the timing and sequence of therapies and the role of radiotherapy for unresectable PDAC.

Stochastic Evolution of Pancreatic Cancer Metastases During Logistic Clonal Expansion.

Despite recent progress in diagnostic and multimodal treatment approaches, most cancer deaths are still caused by metastatic spread and the subsequent growth of tumor cells in sites distant from the primary organ. So far, few quantitative studies are available that allow for the estimation of metastatic parameters and the evaluation of alternative treatment strategies. Most computational studies have focused on situations in which the tumor cell population expands exponentially over time; however, tumors may eventually be subject to resource and space limitations so that their growth patterns deviate from exponential growth to adhere to density-dependent growth models.

Nuclear topology modulates the mutational landscapes of cancer genomes.

Nuclear organization of genomic DNA affects processes of DNA damage and repair, yet its effects on mutational landscapes in cancer genomes remain unclear. Here we analyzed genome-wide somatic mutations from 366 samples of six cancer types. We found that lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core.

mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors.

Although agents that inhibit specific oncogenic kinases have been successful in a subset of cancers, there are currently few treatment options for malignancies that lack a targetable oncogenic driver. Nevertheless, during tumor evolution cancers engage a variety of protective pathways, which may provide alternative actionable dependencies. Here, we identify a promising combination therapy that kills -mutant tumors by triggering catastrophic oxidative stress.

Electrochemical Corrosion Behavior of Ta₂N Nanoceramic Coating in Simulated Body Fluid.

In order to improve the corrosion and wear resistance of biomedical Ti-6Al-4V implants, a Ta₂N nanoceramic coating was synthesized on a Ti-6Al-4V substrate by the double glow discharge plasma process. The Ta₂N coating, composed of fine nanocrystals, with an average grain size of 12.8 nm, improved the surface hardness of Ti-6Al-4V and showed good contact damage tolerance and good adhesion strength to the substrate.

Immune Escape in Breast Cancer During to Invasive Carcinoma Transition.

To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45CD3 T cells demonstrated a decrease in CD8 signatures in IDCs.

Probabilistic Modeling of Reprogramming to Induced Pluripotent Stem Cells.

Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is typically an inefficient and asynchronous process. A variety of technological efforts have been made to accelerate and/or synchronize this process. To define a unified framework to study and compare the dynamics of reprogramming under different conditions, we developed an in silico analysis platform based on mathematical modeling.

Electrochemical Corrosion Behavior of Nanocrystalline β-Ta Coating for Biomedical Applications.

To explore its potential as a highly corrosion-resistant coating for biomedical titanium alloys, a novel β-Ta nanocrystalline coating, composed of equiaxed β-Ta grains with an average grain size ∼22 nm, was deposited onto Ti-6Al-4V substrate using a double glow discharge plasma technique. The newly developed coating exhibited an extremely dense and homogeneous microstructure, exhibiting a strong (002) preferred orientation. The electrochemical behavior and semiconducting properties, such as donor density, flat-band potential, and diffusivity of point defects (), of the passive film formed on the β-Ta coating were compared to those for both uncoated Ti-6Al-4V and commercially pure Ta in Ringer's physiological solution at 37 °C, using an array of complementary electrochemical techniques.

Bacillus licheniformis trehalose-6-phosphate hydrolase structures suggest keys to substrate specificity.

Trehalose-6-phosphate hydrolase (TreA) belongs to glycoside hydrolase family 13 (GH13) and catalyzes the hydrolysis of trehalose 6-phosphate (T6P) to yield glucose and glucose 6-phosphate. The products of this reaction can be further metabolized by the energy-generating glycolytic pathway. Here, crystal structures of Bacillus licheniformis TreA (BlTreA) and its R201Q mutant complexed with p-nitrophenyl-α-D-glucopyranoside (R201Q-pPNG) are presented at 2.

The mathematics of cancer: integrating quantitative models.

Mathematical modelling approaches have become increasingly abundant in cancer research. The complexity of cancer is well suited to quantitative approaches as it provides challenges and opportunities for new developments. In turn, mathematical modelling contributes to cancer research by helping to elucidate mechanisms and by providing quantitative predictions that can be validated.

Dose-Dependent Mutation Rates Determine Optimum Erlotinib Dosing Strategies for EGFR Mutant Non-Small Cell Lung Cancer Patients.

Background: The advent of targeted therapy for cancer treatment has brought about a paradigm shift in the clinical management of human malignancies. Agents such as erlotinib used for EGFR-mutant non-small cell lung cancer or imatinib for chronic myeloid leukemia, for instance, lead to rapid tumor responses. Unfortunately, however, resistance often emerges and renders these agents ineffective after a variable amount of time.

An Evolutionary Approach for Identifying Driver Mutations in Colorectal Cancer.

The traditional view of cancer as a genetic disease that can successfully be treated with drugs targeting mutant onco-proteins has motivated whole-genome sequencing efforts in many human cancer types. However, only a subset of mutations found within the genomic landscape of cancer is likely to provide a fitness advantage to the cell. Distinguishing such "driver" mutations from innocuous "passenger" events is critical for prioritizing the validation of candidate mutations in disease-relevant models.

Heterogeneous nucleation helps the search for initial crystallization conditions of γ-glutamyl transpeptidase from Bacillus licheniformis.

Here, the crystallization and preliminary X-ray diffraction studies of Bacillus licheniformis γ-glutamyl transpeptidase (BlGT) are reported. The serendipitous finding of heterogeneous nucleants in the initial experiments provided the first crystallization conditions for the protein. Crystals were grown by hanging-drop vapour diffusion using a precipitant solution consisting of 20%(w/v) PEG 3350, 0.

Olanzapine-divalproex combination versus divalproex monotherapy in the treatment of bipolar mixed episodes: a double-blind, placebo-controlled study.

Objective: This 6-week, randomized, double-blind, placebo-controlled trial used simultaneous depression and mania criteria to compare a single mood stabilizer, divalproex, with and without adjunctive olanzapine in patients with bipolar I disorder experiencing acute mixed episodes.

Method: Two hundred two adults, aged 18 to 60 years, who met DSM-IV-TR criteria for bipolar disorder with a current mixed episode and had been taking divalproex for >or=14 days at levels of 75 to 125 microg/mL with inadequate efficacy (21-item Hamilton Depression Rating Scale [HDRS-21] and Young Mania Rating Scale [YMRS] scores >or=16) were randomly assigned to olanzapine 5 to 20 mg/d versus placebo augmentation. HDRS-21, YMRS, Clinical Global Impressions for Bipolar Disorder (CGI-BP), hospitalizations, concomitant medications, and adverse events were assessed.

Combined IFN-gamma-endostatin gene therapy and radiotherapy attenuates primary breast tumor growth and lung metastases via enhanced CTL and NK cell activation and attenuated tumor angiogenesis in a murine model.

Background: Gene-radiotherapy, a combination of gene therapy and radiotherapy, is a new paradigm for cancer treatment, with the potential to simultaneously improve local and systemic breast cancer control. The aim of this study was to evaluate antitumor effect of interferon (IFN)-gamma-endostatin-based gene-radiotherapy in a murine metastatic breast tumor model, and to elucidate possible mechanisms involved.

Methods: Murine mammary adenocarcinoma 4T1 cells transfected with pEgr-IFN-gamma and pEgr-endostatin plasmids were irradiated (2-20 Gy).

Taurolidine induces apoptosis of murine melanoma cells in vitro and in vivo by modulation of the Bcl-2 family proteins.

Background: This study evaluates whether taurolidine, a novel antibiotic agent, induces murine melanoma cell apoptosis in vitro and in vivo.

Methods: Murine melanoma cells (B16 4A5 and B16 F10) were treated with taurolidine (0-100 microM) for 12 and 24 hr. Cell viability and apoptosis were assessed by MTT assay and FACScan analysis.