Gastrointestinal Diseases
Victor A. Bernstam in Pocket Guide to GENE LEVEL DIAGNOSTICS in Clinical Practice, 2019
Molecular cytogenetic approaches hold the promise of developing the least invasive means of objective assessment of gastrointestinal diseases. Tumor suppressor genes, known to be consistently altered or deleted in various neoplasias, including those of the gastrointestinal tract, encode products essential for the maintenance of normal growth controls. Normal human gastrointestinal mucosa contains T cell growth factor α and urogastrone epidermal growth factor. Deoxyribonucleic acid (DNA) content has been proposed as an objective criterion for differential diagnosis and/or prognosis of colorectal neoplasias. In adenocarcinomas histopathological evaluation suggested that DNA content can be used for prognostic purposes: a better prognosis could be entertained for cases of polyploid DNA content of carcinomas compared to those with an aneuploid pattern. Multiple sampling is strongly advocated to reduce the effects of marked heterogeneity of ploidy characteristics in individual samples from colorectal carcinomas. DNA ploidy assessment has some prognostic value in gastric carcinomas, but only in advanced tumors with lymph node metastases.
POLYPLOIDY
Hugh Fletcher, Ivor Hickey, Paul Winter, Paul Winter in BIOS Instant Notes in Genetics, 2002
Polyploidy has been important for providing spare copies of genes which can evolve new functions. Comparisons of whole genomes provides evidence of complete genome duplication (tetraploidization) in Saccharomyces yeasts and also of doublings early in the development of multicellular animals and again in early tetrapods. There are also numerous duplications of small chromosome segments. Usually, one of the two copies of each duplicated gene either mutates and is lost, or rapidly diverges and acquires a new function.
Silks Produced by Insect Labial Glands
Prof. Dr. Thomas Scheibel in Fibrous Proteins, 2008
Insect silks are secreted from diverse gland types; this chapter deals with the silks produced by labial glands of Holometabola (insects with pupa in their life cycle). Labial silk glands are composed of a few tens or hundreds of large polyploid cells that secrete polymerizing pro teins which are stored in the gland lumen as a semi-liquid gel. Polymerization is based on weak molecular interactions between repetitive amino acid motifs present in one or more silk proteins; cross-linking by disulfide bonds may be important in the silks spun under water. The mechanism of long-term storage of the silk dope inside the glands and its conversion into the silk fiber during spinning is not fully understood. The conversion occurs within seconds at ambient temperature and pressure, under minimal drawing force and in some cases under water. The silk filament is largely built of proteins called fibroins and in Lepidoptera and Trichoptera coated by glue-type proteins known as sericins. Silks often contain small amounts of additional proteins of poorly known function. The silk components controlling dope storage and filament formation seem to be conserved at the level of orders, while the nature of polymerizing motifs in the fibroins, which determine the physical properties of silk, differ at the level of family and even genus. Most silks are based on fibroin ß-sheets interrupted with other structures such as α -helices but the silk proteins of certain sawflies have predominantly a collagen-like or polyglycine II arrangement and the silks of social Hymenoptera are formed from proteins in a coiled coil arrangement.
Centrosome Abnormalities and Polyploidy in Murine Mammary Carcinomas with Different Degrees of Hormone Responsiveness
Published in Cancer Investigation, 2020
Melina Bilinski, Claudia Lanari, Victoria T. Fabris
Centrosome amplification leads to aberrant mitosis, giving rise to aneuploidy and it has been associated with poor prognosis in human cancers. This study aimed to evaluate the relationship between polyploidy, centrosome abnormalities, and response to endocrine treatment in progestin-induced mouse mammary carcinomas. We found cells with three or more centrosomes in the polyploid tumors. The endocrine unresponsive tumors showed a higher average number of centrosomes per cell than the responsive tumors. The results suggest an association between polyploidy and centrosome amplification with the resistance to endocrine therapy in this luminal breast cancer model.
Belinostat and vincristine demonstrate mutually synergistic cytotoxicity associated with mitotic arrest and inhibition of polyploidy in a preclinical model of aggressive diffuse large B cell lymphoma
Published in Cancer Biology & Therapy, 2016
Aaron P. Havas, Kameron B. Rodrigues, Anvi Bhakta, Joseph A. Demirjian, Seongmin Hahn, Jack Tran, Margarethakay Scavello, Ana A. Tula-Sanchez, Yi Zeng, Monika Schmelz, Catharine L. Smith
Diffuse Large B-cell lymphoma (DLBCL) is an aggressive malignancy that has a 60 percent 5-year survival rate, highlighting a need for new therapeutic approaches. Histone deacetylase inhibitors (HDACi) are novel therapeutics being clinically-evaluated in combination with a variety of other drugs. However, rational selection of companion therapeutics for HDACi is difficult due to their poorly-understood, cell-type specific mechanisms of action. To address this, we developed a pre-clinical model system of sensitivity and resistance to the HDACi belinostat using DLBCL cell lines. In the current study, we demonstrate that cell lines sensitive to the cytotoxic effects of HDACi undergo early mitotic arrest prior to apoptosis. In contrast, HDACi-resistant cell lines complete mitosis after a short delay and arrest in G1. To force mitotic arrest in HDACi-resistant cell lines, we used low dose vincristine or paclitaxel in combination with belinostat and observed synergistic cytotoxicity. Belinostat curtails vincristine-induced mitotic arrest and triggers a strong apoptotic response associated with downregulated MCL-1 expression and upregulated BIM expression. Resistance to microtubule targeting agents (MTAs) has been associated with their propensity to induce polyploidy and thereby increase the probability of genomic instability that enables cancer progression. Co-treatment with belinostat effectively eliminated a vincristine-induced, actively cycling polyploid cell population. Our study demonstrates that vincristine sensitizes DLBCL cells to the cytotoxic effects of belinostat and that belinostat prevents polyploidy that could cause vincristine resistance. Our findings provide a rationale for using low dose MTAs in conjunction with HDACi as a potential therapeutic strategy for treatment of aggressive DLBCL.
Different cell fates after mitotic slippage: From aneuploidy to polyploidy
Published in Molecular & Cellular Oncology, 2016
The molecular mechanism responsible for cell fate after mitotic slippage remains unclear. We investigated the different postmitotic effects of aneuploidy versus polyploidy using chemical inhibitors of centromere-associated protein-E (CENP-E) and kinesin family member 11 (KIF11, also known as Eg5). Aneuploidy caused substantial proteotoxic stress and DNA damage accompanied by p53-mediated postmitotic apoptosis, whereas polyploidy did not induce these antiproliferative effects.
Related Knowledge Centers
- Chromosome Aberrations
- Chromosome Disorders
- Holoprosencephaly
- Xxy
- Multiple Abnormalities
- Ploidies
- Miscarrages