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Pleomorphic Anaplastic Neuroblastoma
Pleomorphic anaplastic neuroblastoma (PAN) is a striking aspect of neuroblastoma first described by Cozzutto and Carbone in 1988.Cozzutto C, Carbone A (1988). Pleomorphic (Anaplastic) neuroblastoma. Arch Pathol Lab Med 112:621-625. Another case was thereafter reported by Cowan, et al. with cytogenetic and immunohistological analysis in a 28-year-old man. The case described by Navarro, et al. showed MYCN amplification (more than 10 copies) and a 1p36 deletion as measured with Fluorescence in situ hybridization, FISH in 13% of cells. Additionally there was a main cell population with a DNA index of 2 indicating a tetraploid DNA content and a high expression of MIBI (Ki-67), bel 2, p53, and P-glycoprotein, either correlated with rapid progression of disease. __TOC__ Histopathology Appearance of focal or diffuse presence of Pleomorphism (cytology), pleomorphic and anaplasia, anaplastic cells is the hallmark of this neuroblastoma variant.Fletcher CDM (2007). Diagnostic Histopatholoy of t ...
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Neuroblastoma
Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the abdomen, neck, or chest, or a painless bluish lump under the skin. Typically, neuroblastoma occurs due to a genetic mutation occurring during early development. Rarely, it may be due to a mutation inherited from a person's parents. Environmental factors have not been found to be involved. Diagnosis is based on a tissue biopsy. Occasionally, it may be found in a baby by ultrasound during pregnancy. At diagnosis, the cancer has usually already spread. The cancer is divided into low-, intermediate-, and high-risk groups based on a child's age, cancer stage, and what the cancer looks like. Treatment and outcomes depends on the risk group a person is in. Treatments may include observation, surgery, radiation, chemotherapy, or stem cell t ...
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MYCN
N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the ''MYCN'' gene. Function The ''MYCN'' gene is a member of the MYC family of transcription factors and encodes a protein with a basic helix-loop-helix ( bHLH) domain. This protein is located in the cell nucleus and must dimerize with another bHLH protein in order to bind DNA. N-Myc is highly expressed in the fetal brain and is critical for normal brain development. The ''MYCN'' gene has an antisense RNA, N-cym or ''MYCNOS'', transcribed from the opposite strand which can be translated to form a protein product. N-Myc and ''MYCNOS'' are co-regulated both in normal development and in tumor cells, so it is possible that the two transcripts are functionally related. It has been shown that the antisense RNA encodes for a protein, named NCYM, that has originated ''de novo'' and is specific to human and chimpanzee. This NCYM protein inhibits GSK ...
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Fluorescence In Situ Hybridization
Fluorescence ''in situ'' hybridization (FISH) is a molecular cytogenetic technique that uses fluorescent probes that bind to only particular parts of a nucleic acid sequence with a high degree of sequence complementarity. It was developed by biomedical researchers in the early 1980s to detect and localize the presence or absence of specific DNA sequences on chromosomes. Fluorescence microscopy can be used to find out where the fluorescent probe is bound to the chromosomes. FISH is often used for finding specific features in DNA for use in genetic counseling, medicine, and species identification. FISH can also be used to detect and localize specific RNA targets (mRNA, lncRNA and miRNA) in cells, circulating tumor cells, and tissue samples. In this context, it can help define the spatial-temporal patterns of gene expression within cells and tissues. Probes – RNA and DNA In biology, a probe is a single strand of DNA or RNA that is complementary to a nucleotide sequence o ...
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Tetraploid
Polyploidy is a condition in which the cells of an organism have more than one pair of ( homologous) chromosomes. Most species whose cells have nuclei (eukaryotes) are diploid, meaning they have two sets of chromosomes, where each set contains one or more chromosomes and comes from each of two parents, resulting in pairs of homologous chromosomes between sets. However, some organisms are polyploid. Polyploidy is especially common in plants. Most eukaryotes have diploid somatic cells, but produce haploid gametes (eggs and sperm) by meiosis. A monoploid has only one set of chromosomes, and the term is usually only applied to cells or organisms that are normally diploid. Males of bees and other Hymenoptera, for example, are monoploid. Unlike animals, plants and multicellular algae have life cycles with two alternating multicellular generations. The gametophyte generation is haploid, and produces gametes by mitosis, the sporophyte generation is diploid and produces spores by meio ...
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P-glycoprotein
P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. More formally, it is an ATP-dependent efflux pump with broad substrate specificity. It exists in animals, fungi, and bacteria, and it likely evolved as a defense mechanism against harmful substances. P-gp is extensively distributed and expressed in the intestinal epithelium where it pumps xenobiotics (such as toxins or drugs) back into the intestinal lumen, in liver cells where it pumps them into bile ducts, in the cells of the proximal tubule of the kidney where it pumps them into urinary filtrate (in the proximal tubule), and in the capillary endothelial cells composing the blood–brain barrier and blood–testis barrier, where it pumps them back into the capillar ...
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Pleomorphism (cytology)
Pleomorphism is a term used in histology and cytopathology to describe variability in the size, shape and staining of cells and/or their nuclei. Several key determinants of cell and nuclear size, like ploidy and the regulation of cellular metabolism, are commonly disrupted in tumors. Therefore, cellular and nuclear pleomorphism is one of the earliest hallmarks of cancer progression and a feature characteristic of malignant neoplasms and dysplasia. Certain benign cell types may also exhibit pleomorphism, e.g. neuroendocrine cells, Arias-Stella reaction. A rare type of rhabdomyosarcoma that is found in adults is known as pleomorphic rhabdomyosarcoma. Despite the prevalence of pleomorphism in human pathology, its role in disease progression is unclear. In epithelial tissue, pleomorphism in cellular size can induce packing defects and disperse aberrant cells. But the consequence of atypical cell and nuclear morphology in other tissues is unknown. See also *Anaplasia *Cell growt ...
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Anaplasia
Anaplasia (from grc, ἀνά ''ana'', "backward" + πλάσις ''plasis'', "formation") is a condition of cells with poor cellular differentiation, losing the morphological characteristics of mature cells and their orientation with respect to each other and to endothelial cells. The term also refers to a group of morphological changes in a cell (nuclear pleomorphism, altered nuclear-cytoplasmic ratio, presence of nucleoli, high proliferation index) that point to a possible malignant transformation. Such loss of structural differentiation is especially seen in most, but not all, malignant neoplasms. Sometimes, the term also includes an increased capacity for multiplication. Lack of differentiation is considered a hallmark of aggressive malignancies (for example, it differentiates leiomyosarcomas from leiomyomas). The term ''anaplasia'' literally means "to form backward". It implies dedifferentiation, or loss of structural and functional differentiation of normal cells. It is n ...
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Pathognomonic
Pathognomonic (rare synonym ''pathognomic'') is a term, often used in medicine, that means "characteristic for a particular disease". A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doubt. Labelling a sign or symptom "pathognomonic" represents a marked intensification of a "diagnostic" sign or symptom. The word is an adjective of Greek origin derived from πάθος ''pathos'' "disease" and γνώμων ''gnomon'' "indicator" (from γιγνώσκω ''gignosko'' "I know, I recognize"). Practical use While some findings may be classic, typical or highly suggestive in a certain condition, they may not occur ''uniquely'' in this condition and therefore may not directly imply a specific diagnosis. A pathognomonic sign or symptom has very high positive predictive value but does not need to have high sensitivity: for example it can sometimes be absent in a certain disease, since the term only implies that, when it is prese ...
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Footnotes
A note is a string of text placed at the bottom of a page in a book or document or at the end of a chapter, volume, or the whole text. The note can provide an author's comments on the main text or citations of a reference work in support of the text. Footnotes are notes at the foot of the page while endnotes are collected under a separate heading at the end of a chapter, volume, or entire work. Unlike footnotes, endnotes have the advantage of not affecting the layout of the main text, but may cause inconvenience to readers who have to move back and forth between the main text and the endnotes. In some editions of the Bible, notes are placed in a narrow column in the middle of each page between two columns of biblical text. Numbering and symbols In English, a footnote or endnote is normally flagged by a superscripted number immediately following that portion of the text the note references, each such footnote being numbered sequentially. Occasionally, a number between brack ...
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