A Method of Limited Replication for the Efficient In Vivo Delivery of Adenovirus to Cancer Cells

Overview summary Replication-defective viral vectors are limited in their ability to diffuse through tissue. This poses a problem for treating tumors in vivo using gene transfer. This article demonstrates that limited replication of adenovirus leads to greater gene transfer efficiency in vitro and in vivo without introducing additional safety concerns beyond traditional adenovirus administration. This has implications for the improvement of current gene transfer methods for treating cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63280/1/hum.1998.9.8-1209.pd

Biological and clinical significance of cancer stem cell plasticity

In the past decade, the traditional view of cancers as a homogeneous collection of malignant cells is being replaced by a model of ever increasing complexity suggesting that cancers are complex tissues composed of multiple cell types. This complex model of tumorigenesis has been well supported by a growing body of evidence indicating that most cancers including those derived from blood and solid tissues display a hierarchical organization of tumor cells with phenotypic and functional heterogeneity and at the apex of this hierarchy are cells capable of self‐renewal. These “tumor imitating cells” or “cancer stem cells” drive tumorigenesis and contribute to metastasis, treatment resistance and tumor relapse. Although tumor stem cells themselves may display both genetic and phenotypic heterogeneity, recent studies have demonstrated that cancer stem cells maintain plasticity to transition between mesenchymal‐like (EMT) and epithelial‐like (MET) states, which may be regulated by the tumor microenvironment. These stem cell state transitions may play a fundamental role in tumor progression and treatment resistance. In this review, we discuss the emerging knowledge regarding the plasticity of cancer stem cells with an emphasis on the signaling pathways and noncoding RNAs including microRNAs (miRNA) and long non‐coding RNAs (lncRNAs) in regulation of this plasticity during tumor growth and metastasis. Lastly, we point out the importance of targeting both the EMT and MET states of CSCs in order to eliminate these lethal seeds of cancers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155480/1/ctm2s4016901400323.pd

Symmetric Division of Cancer Stem Cells – a Key Mechanism in Tumor Growth that should be Targeted in Future Therapeutic Approaches

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109781/1/cpt6100202.pd

Mammary stem cell number as a determinate of breast cancer risk

The 'cancer stem cell hypothesis' posits that cancers, including breast cancer, arise in tissue stem or progenitor cells. If this is the case, then it follows that the risk for developing breast cancer may be determined in part by the number of breast stem/progenitor cells that can serve as targets for transformation. Stem cell number may be set during critical windows of development, including in utero, adolescence, and pregnancy. The growth hormone/insulin-like growth factor-1 axis may play an important role in regulating breast stem cell number during these developmental windows, suggesting an important link between this signaling pathway and breast cancer risk

PENGEMBANGAN PERANGKAT PEMBELAJARAN MATEMATIKA BERBASIS KARAKTER PADA PEMBELAJARAN QUANTUM POKOK BAHASAN PERSAMAAN GARIS LURUS SMP KELAS VIII

Abstract. Quantum Teaching is a concept that describes the new ways to facilitate the learning process. This concept has been widely used in a class to improve the student achievement. Type of this research is a developmental research by using 4-D model, it consists 4 steps namely define, design, develop, and disseminate. The subject of a research is an equation of straight line for grade VIII A of SMP Negeri 1 Maesan. The data collection methods used in this research are validation, observation, questionnaire, and test. The result of the research are Sillaby, Teaching Plan, Teacher Book, Student Book, Work Sheet, and achievement test. All the learning materials obtained from this research satisfy the effectiveness criteria and the student achievement is 85.18% of student get score bigger than 60. Key Words : Developmental Research, Characters, Quantum Teaching, 4-D model

Identification of murine mammary stem cells: implications for studies of mammary development and carcinogenesis

The epithelial components of the mammary gland are thought to arise from a stem cell capable of both self-renewal and multi-lineage differentiation. Furthermore, there is increasing evidence that mammary carcinomas originate in these cells or their immediate progeny. The recent identification of murine mammary stem cells should facilitate their molecular characterization and help to elucidate their role in mammary carcinogenesis. In addition, an understanding of the biology of these cells including the pathways that regulate their self-renewal and differentiation may suggest new approaches for the prevention and treatment of breast cancer

An improved PKPD modeling approach to characterize the pharmacodynamic interaction over time between ceftazidime/avibactam and colistin from in vitro time-kill experiments against multidrug-resistant Klebsiella pneumoniae isolates.

In contrast to the checkerboard method, bactericidal experiments [time-kill curves (TKCs)] allow an assessment of pharmacodynamic (PD) interactions over time. However, TKCs in combination pose interpretation problems. The objective of this study was to characterize the PD interaction over time between ceftazidime/avibactam (CZA) and colistin (CST) using TKC against four multidrug-resistant Klebsiella pneumoniae susceptible to both antibiotics and expressing a widespread carbapenemase determinant KPC-3. In vitro TKCs were performed and analyzed using pharmacokinetic/pharmacodynamic (PKPD) modeling. The general pharmacodynamic interaction model was used to characterize PD interactions between drugs. The 95% confidence intervals (95%CIs) of the expected additivity and of the observed interaction were built using parametric bootstraps and compared to evaluate the in vitro PD interaction over time. Further simulations were conducted to investigate the effect of the combination at varying concentrations typically observed in patients. Regrowth was observed in TKCs at high concentrations of drugs alone [from 4 to 32× minimum inhibitory concentrations (MIC)], while the combination systematically prevented the regrowth at concentrations close to the MIC. Significant synergy or antagonism were observed under specific conditions but overall 95%CIs overlapped widely over time indicating an additive interaction between antibiotics. Moreover, simulations of typical PK profile at standard dosages indicated that the interaction should be additive in clinical conditions. The nature of the PD interaction varied with time and concentration in TKC. Against the four K. pneumoniae isolates, the bactericidal effect of CZA + CST combination was predicted to be additive and to prevent the emergence of resistance at clinical concentrations

Regulatory Roles of miRNA in the Human Neural Stem Cell Transformation to Glioma Stem Cells

To investigate the expressional alternation of microRNAs (miRNA) during the malignant transformation and development of human glioma, we measured miRNA expression profile as well as mRNA expression profile in normal human neural stem cells (hNSCs) and human glioma stem cells (hGSCs). We found 116 miRNA up‐regulated and 62 miRNA down‐regulated in GSCs. On the other hand, we identified 1,372 mRNA down‐regulated, and 1,501 mRNA up‐regulated in GSCs compared to those in NSCs. We then analyzed the pathways and the predicted target genes of the miRNAs which differ significantly in expression between GSCs and NSCs using the statistical enrichment methods. These target mRNAs are involved in many cancer‐related signaling pathways, such as cell cycle, axon guidance, glioma development, adhesion junction, MAPK and Wnt signaling. Furthermore, we obtained the differently expressed miRNA‐target relationships according to the θ value which is used to calculate the regulation extent of miRNA‐target and using the databases of miRanda, Targetscans and Pictar. Among the top 10 miRNA‐target relationships, hsa‐miR‐198 and its potential targeted gene DCX and NNAT were selected for validation, and NNAT was found to be the direct target of miR‐198. Finally, the functional roles of miR‐155–5p and miR‐124–3p whose expressions altered significantly between GSCs and NSCs were addressed. Our results provide new clues for the potential mechanisms involved in the origin and development of glioma. Clinically, the altered miRNAs may serve as potential targets and diagnostic tools for novel therapeutic strategies of glioblastoma. J. Cell. Biochem. 115: 1368–1380, 2014. © 2014 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107550/1/jcb24786.pd