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Perez Alamino R.,Health Science Center | Espinoza L.R.,Health Science Center | Zea A.H.,Stanley ott Cancer Center
Clinical Rheumatology

IgG4-related disease is defined as a multi-organ systemic disorder with pathological findings affecting a wide range of organ systems. The condition unifies a large number of clinical diagnoses previously considered as being confined to single organ systems. At present, several issues related to its pathophysiology remained controversial, including the natural history of the disease, the pathogenic role of IgG4, and its use as a biomarker. Glucocorticoids are considered the treatment of choice for remission induction of IgG4-related disease manifestations; however, concerns regarding duration of therapy and management of refractory disease remained to be elucidated. © 2013 Clinical Rheumatology. Source

Alahari S.K.,Stanley ott Cancer Center
Journal of Visualized Experiments

Cell migration is a dynamic process, which is important for embryonic development, tissue repair, immune system function, and tumor invasion 1, 2. During directional migration, cells move rapidly in response to an extracellular chemotactic signal, or in response to intrinsic cues 3 provided by the basic motility machinery. Random migration occurs when a cell possesses low intrinsic directionality, allowing the cells to explore their local environment. Cell migration is a complex process, in the initial response cell undergoes polarization and extends protrusions in the direction of migration 2. Traditional methods to measure migration such as the Boyden chamber migration assay is an easy method to measure chemotaxis in vitro, which allows measuring migration as an end point result. However, this approach neither allows measurement of individual migration parameters, nor does it allow to visualization of morphological changes that cell undergoes during migration. Here, we present a method that allows us to monitor migrating cells in real time using video - time lapse microscopy. Since cell migration and invasion are hallmarks of cancer, this method will be applicable in studying cancer cell migration and invasion in vitro. Random migration of platelets has been considered as one of the parameters of platelet function 4, hence this method could also be helpful in studying platelet functions. This assay has the advantage of being rapid, reliable, reproducible, and does not require optimization of cell numbers. In order to maintain physiologically suitable conditions for cells, the microscope is equipped with CO 2 supply and temperature thermostat. Cell movement is monitored by taking pictures using a camera fitted to the microscope at regular intervals. Cell migration can be calculated by measuring average speed and average displacement, which is calculated by Slidebook software. © JoVE 2006-2012. Source

Stalder M.W.,Louisiana State University Health Sciences Center | Anthony C.T.,Louisiana State University Health Sciences Center | Woltering E.A.,Louisiana State University Health Sciences Center | Woltering E.A.,Stanley ott Cancer Center
Journal of Surgical Research

Background: High doses (10 nM) of epothilone B, a microtubule stabilizer, will inhibit the development of human tumor-derived angiogenesis following short (14 d) drug exposure times. Metronomic dosing regimes use lower drug doses and prolonged drug exposure times in an attempt to decrease toxicity compared with standard dosing schedules. We hypothesized that epothilone B would be an effective anti-angiogenic agent when administered at very low doses over an extended period of time. Methods: Fragments of four fresh human tumors were cultured in a fibrin-thrombin matrix and maintained in nutrient media plus 20% fetal bovine serum (FBS) for 56 d. Tumor fragments (n = 40-60 per group) were exposed to weekly doses of epothilone B at concentrations of 10, 5, 1, 0.5, or 0.1 nM. All of these concentrations are clinically achievable. Tumor angiogenesis was assessed weekly on d 14-56 using a validated visual grading system. This system rates neovessel growth, density, and length on a 0-16 scale [angiogenic index, (AI)]. The average change in AI between d 14 and 56 was calculated for all samples and used to evaluate the metronomic response. Results: Epothilone B produced a dose-dependent anti-angiogenic response in all tumors. Two of the four tumors demonstrated a clear and significant metronomic anti-angiogenic effect over time. Conclusions: Epothilone B, when dosed by a metronomic schedule may have a significant anti-angiogenic effect on human solid tumors. This study provides evidence for the potential use of epothilone B on a metronomic dosing schedule. © 2011 Elsevier Inc. All rights reserved. Source

Cuchacovich R.,Health Science Center | Perez-Alamino R.,Health Science Center | Zea A.H.,Stanley ott Cancer Center | Espinoza L.R.,Health Science Center
Clinical Rheumatology

Psoriatic arthritis (PsA) is a systemic inflammatory condition associated with psoriasis. Despite considerable heterogeneity in clinical presentation, genetic studies and animal models support the notion that PsA is a distinct disease. We aimed to characterize the PsA genotype by gene expression profile and to research the effect in gene modulation of methotrexate (MTX) and TNF-inhibitors (TNF-I) in PsA-treated patients. Nine PsA patients, according to CASPAR criteria, and three healthy controls were recruited from an outpatient rheumatology clinic. Three out of nine PsA patients were naïve to treatment, three received TNF-I, and the remaining three were on MTX-monotherapy. Blood samples were collected and analyzed by human genome U95 Array-Affymetrix (GeneChip® instrument system). Identification of statistically significant differences between differentially expressed genes was determined by Mann–Whitney and t test (p < 0.05). The microarray profile identified a predominance of differentially expressed genes with an increased expression in baseline PsA patients: 115/12,000 genes were up-regulated and 13/12,000 down-regulated, as compared to healthy controls. The great majority were involved in inflammatory cells and pathways. In the biologic-treated patients, a higher number of down-regulated genes were expressed vs. the MTX patients, 161 vs. 33, respectively. This study shows that in PsA patients, TNF-I and MTX are able to modulate the gene expression in a synergistic and additive manner. © 2014, International League of Associations for Rheumatology (ILAR). Source

Alahari S.,Stanley ott Cancer Center
MicroRNA in Cancer

The field of microRNA biology is really emerging in the last couple of years. Several investigators highlighted the importance of miRNAs in cancer. Although there is so much literature on microRNAs exist, a comprehensive book is still not available. Thus this book will be a great use to the scientists in the field of cancer biology. In addition, this book will be a good source of information for undergraduate, graduate students who want to develop their research careers in cancer biology. © 2013 Springer Science+Business Media Dordrecht. Source

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