Fibroblasts—a key host cell type in tumor initiation, progression, and metastasis

Tumor initiation, growth, invasion, and metastasis occur as a consequence of a complex interplay between the host environment and cancer cells. Fibroblasts are now recognized as a key host cell type involved in host–cancer signaling. This review discusses some recent studies that highlight the roles of fibroblasts in tumor initiation, early progression, invasion, and metastasis. Some clinical studies describing the prognostic significance of fibroblast-derived markers and signatures are also discussed

Rationale and design of a randomized controlled trial of directly observed hepatitis C treatment delivered in methadone clinics

<p>Abstract</p> <p>Background</p> <p>Most methadone-maintained injection drug users (IDUs) have been infected with hepatitis C virus (HCV), but few initiate HCV treatment. Physicians may be reluctant to treat HCV in IDUs because of concerns about treatment adherence, psychiatric comorbidity, or ongoing drug use. Optimal HCV management approaches for IDUs remain unknown. We are conducting a randomized controlled trial in a network of nine methadone clinics with onsite HCV care to determine whether modified directly observed therapy (mDOT), compared to treatment as usual (TAU), improves adherence and virologic outcomes among opioid users.</p> <p>Methods/Design</p> <p>We plan to enroll 80 HCV-infected adults initiating care with pegylated interferon alfa-2a (IFN) plus ribavirin, and randomize them to mDOT (directly observed daily ribavirin plus provider-administered weekly IFN) or TAU (self-administered ribavirin plus provider-administered weekly IFN). Our outcome measures are: 1) self-reported and pill count adherence, and 2) end of treatment response (ETR) or sustained viral response (SVR). We will use mixed effects linear models to assess differences in pill count adherence between treatment arms (mDOT v. TAU), and we will assess differences between treatment arms in the proportion of subjects with ETR or SVR with chi square tests. Of the first 40 subjects enrolled: 21 have been randomized to mDOT and 19 to TAU. To date, the sample is 77% Latino, 60% HCV genotype-1, 38% active drug users, and 27% HIV-infected. Our overall retention rate at 24 weeks is 92%, 93% in the mDOT arm and 92% in the TAU arm.</p> <p>Discussion</p> <p>This paper describes the design and rationale of a randomized clinical trial comparing modified directly observed HCV therapy delivered in a methadone program to on-site treatment as usual. Our trial will allow rigorous evaluation of the efficacy of directly observed HCV therapy (both pegylated interferon and ribavirin) for improving adherence and clinical outcomes. This detailed description of trial methodology can serve as a template for the development of future DOT programs, and can also guide protocols for studies among HCV-infected drug users receiving methadone for opiate dependence.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01442311">NCT01442311</a></p

Mouse models of breast cancer metastasis

Metastatic spread of cancer cells is the main cause of death of breast cancer patients, and elucidation of the molecular mechanisms underlying this process is a major focus in cancer research. The identification of appropriate therapeutic targets and proof-of-concept experimentation involves an increasing number of experimental mouse models, including spontaneous and chemically induced carcinogenesis, tumor transplantation, and transgenic and/or knockout mice. Here we give a progress report on how mouse models have contributed to our understanding of the molecular processes underlying breast cancer metastasis and on how such experimentation can open new avenues to the development of innovative cancer therapy

Smoking as a Risk Factor for Nephropathy in Non-Insulin-Dependent Diabetics

This study examines whether there was an association between smoking and nephropathy in patients with non-insulin-dependent diabetes mellitus enrolled in the Appropriate Blood Pressure Control in Diabetes Trial. Sixty-one percent of the patients were smokers; 26% had microalbuminuria, and 14% had overt nephropathy. There was a univariate association between diabetic nephropathy and gender, smoking status, duration of diabetes, hypertension, glycosylated hemoglobin level, creatinine level, body mass index, and cholesterol level. Stepwise logistic regression demonstrated an independent association between smoking and diabetic nephropathy (odds ratio 1.61; 95% confidence interval 1.01, 2.58). These findings may have important implications for patients with non-insulin-dependent diabetes mellitus who smoke

4D Near-Field Source Localization Using Cumulant

This paper proposes a new cumulant-based algorithm to jointly estimate four-dimensional (4D) source parameters of multiple near-field narrowband sources. Firstly, this approach proposes a new cross-array, and constructs five high-dimensional Toeplitz matrices using the fourth-order cumulants of some properly chosen sensor outputs; secondly, it forms a parallel factor (PARAFAC) model in the cumulant domain using these matrices, and analyzes the unique low-rank decomposition of this model; thirdly, it jointly estimates the frequency, two-dimensional (2D) directions-of-arrival (DOAs), and range of each near-field source from the matrices via the low-rank three-way array (TWA) decomposition. In comparison with some available methods, the proposed algorithm, which efficiently makes use of the array aperture, can localize N&#x2212;3 sources using N sensors. In addition, it requires neither pairing parameters nor multidimensional search. Simulation results are presented to validate the performance of the proposed method

Collision Cross Section Calculations Using HPCCS

A technical overview of the High Performance Collision Cross Section (HPCCS) software for accurate and efficient calculations of collision cross sections for molecular ions ranging from small organic molecules to large protein complexes is presented. The program uses helium or nitrogen as buffer gas with considerable gains in computer time compared to publicly available codes under the Trajectory Method approximation. HPCCS is freely available under the Academic Use License at https://github.com/cepid-cces/hpccs .</p