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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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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Another chemotherapy isolated form the fungus Streptomyces verticullus is Bleomycin. Its mechanism of action is similar to that of the anthracyclines, in that free oxygen radicals are formed that result in DNA breaks leading to cancer cell death. This drug is rarely used by itself rather in conjunction with other chemotherapies. Bleomycin is an active agent in regimens for testicular cancer and Hodgkin’s lymphoma. The most concerning side effect of this drug is lung toxicities due to oxygen free radical formation.

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Many of the currently effective anti-cancer drugs are developed from natural sources. The drug daunorubicin was isolated from Streptomyces, a soil-dwelling fungus. Doxorubicin, another anthracycline drug, was isolated from a mutated strain of the same fungus. Both of these drugs have a similar mechanism of action, but the latter is more effective in the treatment of solid tumors. This class of chemotherapeutics works by the formation of free oxygen radicals. These radicals result in DNA strand breaks and subsequent inhibition of DNA synthesis and function. Anthracyclines also inhibit the enzyme topoisomerase by forming a complex with the enzyme and DNA. Topoisomerases are a class of enzymes that serve to unwind the DNA double strand helix to allow for DNA repair, replication and transcription. This class of chemotherapeutics is also not cell cycle specific. The most important side effect of this group of drugs is cardiac toxicity. The same free radicals that serve to damage the DNA of the cancer cell may damage the cells of the heart muscle. Oncologists monitor heart function very carefully when patients are on these medications. Other commonly used anthracyclines include Idarubicin, Epirubicin, and Mitoxantrone.

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In 1948, Dr. Sidney Farber showed that a folic acid analog could induce remission in childhood leukemia. Approximately 10 out of the 16 patients treated demonstrated evidence of hematologic improvement. This experience provided the foundation for scientists to synthesize a number of other agents that either target naturally occurring compounds or inhibit key enzymatic reactions in their biochemical pathways. In general, all antimetabolites interfere with normal metabolic pathways, including those necessary for making new DNA. The most widely used antifolate in cancer therapy, with activity against leukemia, lymphoma, breast cancer, head and neck cancer, sarcomas, colon cancer, bladder cancer and choriocarcinomas, is Methotraxate. Methotraxate inhibits a crucial enzyme required for DNA synthesis and therefore exerts its effect on the S phase of the cell cycle.

5-Fluorouracil (5-FU), another widely used antimetabolite, prevents DNA synthesis by interfering with the nucleotide ( DNA components) production. It, too, has a wide range of activity including colon cancer, breast cancer, head and neck cancer, pancreatic cancer, gastric cancer, anal cancer, esophageal cancer and hepatomas (primary liver tumor). A unique and interesting aspect of this drug is its toxicity profile. 5-Fluorouracil is metabolized by a naturally occurring enzyme in the body called dihydropyrimidine dehydrogenase, or DPD. There is a small population of people who are deficient of this particular enzyme. Lacking DPD does not interfere with normal body function and thus people are not aware that they are lacking it. However, when these patients are given this chemotherapy drug, they are unable to metabolize it and therefore get acute and severe toxicities (side effects). The most often seen toxicities include bone marrow suppression, severe GI toxicities, and neurotoxicities which may include seizures and even coma. It is important for the oncologist to recognize this early and give the patient Thymidine as an antidote. A drug called Capecitabine is an oral type of 5-Fluorouracil compound that has similar side effect potentials.

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Alkylating agents are the oldest class of anticancer drugs. Almost all of these drugs are active or latent nitrogen mustards. Nitrogen mustards are various poisonous compounds originally developed for military use. Alkylating agents all share a common mechanism of action, but differ in their clinical activity. They work by attacking the negatively charged sites on the DNA (oxygen, nitrogen, phosphorous and sulfur atoms). By binding to the DNA, steps (replication, transcription, and base pairing) leading to duplication of the cell’s genetic material are significantly altered. In addition, alkylation of DNA leads to DNA strand breaks and DNA strand cross-linking. By altering DNA in this manner, cellular activity is stopped and the cell dies. Chemotherapy drugs in this class are active in every phase of the cell cycle. As a result, this class of anticancer drugs is very powerful and is used in many types of cancer, including both solid tumors and leukemias.

In general, prolonged use of these drugs will lead decreased sperm production, cessation of menstruation, and possibly cause permanent infertility. This class of chemotherapeutics should never be used in the first trimester of pregnancy as they have been shown to increase fetal malformations. Use in the second or third trimester does not seem to carry the same risk. All alkylating agents can cause secondary cancers although not all agents are equal in their carcinogenic potential. The most common secondary cancer is a type of leukemia (AML, or Acute Myeloid Leukemia) that can occur years after therapy with an alkylating agent.

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Most chemotherapy agents kill cancer cells by affecting DNA synthesis or function, a process that occurs through the cell cycle. Each drug varies in the way this occurs within the cell cycle.

The major categories of chemotherapy agents are alkylating agents, antimetabolites, anthracyclines, plant alkaloids, antitumor antibiotics, taxanes, and platinums. Let’s review the characteristics of these groups.

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