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Positive Regulator Molecules02:39

Positive Regulator Molecules

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Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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M-Cdk Drives Transition Into Mitosis02:15

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Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
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M cyclin...
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Separation of Sister Chromatids02:17

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At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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Differential cyclin-E1 expression in CIC-rearranged sarcoma.

Berna Karabulut1, Fisun Ardic Yukruk1, Sibel Yenidunya1

  • 1Department of Pathology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara 06200, Turkey.

Annals of Diagnostic Pathology
|May 4, 2024
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Summary

Cyclin E1 expression is elevated in CIC-rearranged sarcoma (CRS), a distinct aggressive cancer, compared to Ewing sarcoma (ES). This finding aids in diagnosing non-ES small round cell tumors.

Keywords:
CIC-rearranged sarcomaCyclin E1EWSR1 gene rearrangementEwing sarcomaSmall round cell sarcoma

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Area of Science:

  • Oncology
  • Pathology
  • Molecular Diagnostics

Background:

  • CIC-rearranged sarcoma (CRS) is a high-grade undifferentiated small round cell sarcoma with aggressive behavior.
  • CRS exhibits distinct features from Ewing sarcoma (ES).
  • CCNE1 expression is linked to tumor growth in CIC::DUX4 sarcomas.

Purpose of the Study:

  • To evaluate the diagnostic value of cyclin E1 expression in CRS.
  • To differentiate CRS from ES and other small round cell tumors.

Main Methods:

  • Immunohistochemistry for cyclin E1 on tissue microarrays.
  • Break-apart FISH for EWSR1 and CIC gene rearrangements.
  • Analysis of 40 small round cell tumors, including CRS, ES, and unclassified cases.

Main Results:

  • Cyclin E1 expression was significantly higher in CRS (80%) and unclassified (61.5%) groups compared to ES (4.5%).
  • High cyclin E1 expression correlated with atypical histology, myxoid stroma, low CD99, and metastasis.
  • Cyclin E1 showed 95.5% sensitivity and 66.7% specificity for detecting non-ES cases.

Conclusions:

  • Cyclin E1 immunohistochemistry is a valuable tool for identifying EWSR1-negative undifferentiated small cell sarcomas, especially CRS.
  • Elevated cyclin E1 expression aids in distinguishing CRS from ES.
  • Further research may explore therapeutic targeting of cyclin E1 in CRS.