Asbestos Cancer Update 2010

The differential diagnosis of renal and supra-renal masses firstly depends on the age of the child. Neuroblastoma (NBL) may be seen antenatally or in the newborn period; this tumour has a good prognosis unlike NBL seen in older children (particularly NBL in those aged 2–4 years). Benign renal masses predominate in early infancy but beyond the first year of life Wilms’ tumour is the most common renal malignancy, until adolescence when renal cell carcinoma has similar or increased frequency as children get older. Adrenal adenomas and carcinomas also occur in childhood; these tumours are indistinguishable on imaging but criteria for the diagnosis of adrenal carcinoma include size larger than 5cm, a tendency to invade the inferior vena cava and to metastasise. The most topical dilemmas in the radiological assessment of renal and adrenal tumours are presented. Topics covered include a proposed revision to the staging of NBL, the problems inherent in distinguishing nephrogenic rests from Wilms’ tumour and the current recently altered approach regarding small lung nodules in children with Wilms’ tumour.

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Background

MicroRNAs (miRNAs) are short single stranded noncoding RNAs that suppress gene expression through either translational repression or degradation of target mRNAs. The annealing between messenger RNAs and 5′ seed region of miRNAs is believed to be essential for the specific suppression of target gene expression. One miRNA can have several hundred different targets in a cell. Rapidly accumulating evidence suggests that many miRNAs are involved in cell cycle regulation and consequentially play critical roles in carcinogenesis.

Methodology/Principal Findings

Introduction of synthetic miR-107 or miR-185 suppressed growth of the human non-small cell lung cancer cell lines. Flow cytometry analysis revealed these miRNAs induce a G1 cell cycle arrest in H1299 cells and the suppression of cell cycle progression is stronger than that by Let-7 miRNA. By the gene expression analyses with oligonucleotide microarrays, we find hundreds of genes are affected by transfection of these miRNAs. Using miRNA-target prediction analyses and the array data, we listed up a set of likely targets of miR-107 and miR-185 for G1 cell cycle arrest and validate a subset of them using real-time RT-PCR and immunoblotting for CDK6.

Conclusions/Significance

We identified new cell cycle regulating miRNAs, miR-107 and miR-185, localized in frequently altered chromosomal regions in human lung cancers. Especially for miR-107, a large number of down-regulated genes are annotated with the gene ontology term ‘cell cycle’. Our results suggest that these miRNAs may contribute to regulate cell cycle in human malignant tumors.

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Objective

This article examines the utility of evidentiary pluralism, a research strategy that selects methods in service of content questions, in the context of rehabilitation psychology. Hierarchical views that favor randomized controlled clinical trials (RCTs) over other evidence are discussed, and RCTs are considered as they intersect with issues in the field. RCTs are vital for establishing treatment efficacy, but whether they are uniformly the best evidence to inform practice is critically evaluated.

Conclusions

The authors argue that because treatment is only one of several variables that influence functioning, disability, and participation over time, an expanded set of conceptual and data analytic approaches should be selected in an informed way to support an expanded research agenda in which therapeutic and extratherapeutic influences on rehabilitation processes and outcomes is investigated. The benefits of evidentiary pluralism are considered, including those that help close the gap between the narrower clinical rehabilitation model and a public health disability model.

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‘Blastomas’ are tumors virtually unique to childhood. Controversy surrounds their nomenclature and there is no globally accepted classification. They are thought to arise from immature, primitive tissues that present persistent embryonal elements on histology, affect a younger pediatric population and are usually malignant. The ‘commoner’ blastomas (neuroblastoma, nephroblastoma, hepatoblastoma, medulloblastoma) account for approximately 25% of solid tumors in the pediatric age range. We present examples of the more unusual blastematous pediatric tumors (lipoblastoma, osteoblastoma, chondroblastoma, hemangioblastoma, gonadoblastoma, sialoblastoma, pleuropulmonary blastoma, pancreatoblastoma, pineoblastoma, and medullomyoblastoma) that were recorded in our institution. Although these rare types of blastomas individually account for <1% of pediatric malignancies, collectively they may be responsible for up to 5% of pediatric tumors in a given population of young children. Imaging is often non-specific but plays an important role in their identification, management and follow-up. Some characteristic imaging features at diagnosis, encountered in cases diagnosed and treated in our institution, are described and reviewed.

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Plant alkaloids are a group of chemotherapy agents derived from plant materials. They are broken down into four groups: topoisomerase inhibitors, epipodophyllotoxins, taxanes and vinca alkaloids. Plant alkaloids are cell-cycle specific, but the cycle affected varies from drug to drug.

Camptothecan analogs (also called Topoisomerase I inhibitors) act by forming a complex with Topoisomerase and DNA resulting in the inhibition and function of the Topoisomerase enzyme. The presence of Topoisomerase is required for on-going DNA synthesis. These drugs are used in many solid and liquid tumors. Unlike other classes of chemotherapy, the side effects of this class of drugs vary from drug to drug.

Camptothecins include both irinotecan and topotecan. The parent compound of these agents, first identified in the late 1950’s, is a naturally occurring alkaloid found in the bark and wood of the Chinese tree Camptotheca accuminata, also called the “Happy Tree”.

Etoposide and Teniposide are epipodophyllotoxin chemotherapy agents (also called topoisomerase II inhibitors) that work by similar mechanisms. They are isolated from the May Apple plant and work in the late S and G 2 phases.

The leaves of a periwinkle plant, Vinca rosea, were used by natives of Madagascar to make tea that reportedly improved diabetes. Although it did not affect blood sugar levels in research studies, it was found that the extract killed cells found in leukemias. Isolation and chemical characterization lead to the currently used chemotherapy drugs: vincristine, vinblastine, and vinorelbine. These chemotherapeutics bind to the tubulin and lead to the disruption of the mitotic spindle apparatus. The disruption of mitosis implies that these drugs are active specifically during the M phase of the cell cycle. They have a wide application to many different malignancies and cause neurotoxicity as the most prominent and dose limiting side effect.

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