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Related Concept Videos

Diffusion01:12

Diffusion

216.5K
Diffusion is the passive movement of substances down their concentration gradients—requiring no expenditure of cellular energy. Substances, such as molecules or ions, diffuse from an area of high concentration to an area of low concentration in the cytosol or across membranes. Eventually, the concentration will even out, with the substance moving randomly but causing no net change in concentration. Such a state is called dynamic equilibrium, which is essential for maintaining overall...
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Diffusion01:21

Diffusion

6.3K
Diffusion is a type of passive transport. In passive transport, a substance tends to move from an area of high concentration to an area of low concentration until the concentration is equal across the space. For example, take the diffusion of substances through the air. When someone opens a perfume bottle in a room filled with people, the perfume is at its highest concentration in the bottle and is at its lowest at the edges of the room. The perfume vapor will diffuse, or spread away, from the...
6.3K
Facilitated Diffusion01:16

Facilitated Diffusion

1.2K
The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
1.2K
Behavior of Gas Molecules: Molecular Diffusion, Mean Free Path, and Effusion03:48

Behavior of Gas Molecules: Molecular Diffusion, Mean Free Path, and Effusion

31.2K
Although gaseous molecules travel at tremendous speeds (hundreds of meters per second), they collide with other gaseous molecules and travel in many different directions before reaching the desired target. At room temperature, a gaseous molecule will experience billions of collisions per second. The mean free path is the average distance a molecule travels between collisions. The mean free path increases with decreasing pressure; in general, the mean free path for a gaseous molecule will be...
31.2K
Protein Diffusion in the Membrane01:24

Protein Diffusion in the Membrane

5.5K
Proteins show rotational as well as lateral diffusion across the membrane. The lateral diffusion of proteins was confirmed through the cell fusion experiment where mouse and human cells were fused, resulting in hybrid cells. When the human and mouse cells fused, the specific membrane proteins on human and mouse cells were marked with the red and green-fluorescent markers, respectively. Initially, the red and green fluorescence was located on the respective hemisphere of the cell. As time...
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Diffusion on Chromatography Columns01:07

Diffusion on Chromatography Columns

1.2K
In column chromatography, when an analyte is introduced as a narrow band at the top of the column, the solutes begin to separate and broaden, developing a Gaussian profile. This broadening occurs due to various factors, such as longitudinal diffusion.
Longitudinal diffusion occurs when the solute molecules in the mobile phase diffuse from the more concentrated center of the chromatographic band to the more dilute regions on either side, both towards and against the flow direction. This...
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Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
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Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System

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Repurposing dasatinib for diffuse large B cell lymphoma.

Claudio Scuoppo1,2, Jiguang Wang3, Mirjana Persaud4

  • 1Institute for Cancer Genetics, Columbia University, New York, NY 10032; cs3064@cumc.columbia.edu rd10@cumc.columbia.edu.

Proceedings of the National Academy of Sciences of the United States of America
|August 7, 2019
PubMed
Summary
This summary is machine-generated.

This study repurposed drugs for diffuse large B-cell lymphoma (DLBCL), finding dasatinib effective against many DLBCL cell lines and resistant tumors. Combining dasatinib with PI3K pathway inhibition overcame resistance, suggesting a new treatment strategy.

Keywords:
DLBCLPTENdasatinib

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Area of Science:

  • Oncology
  • Pharmacology
  • Hematology

Background:

  • Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with unmet therapeutic needs.
  • Drug repurposing offers a strategy to identify novel treatments for DLBCL.
  • Existing therapies like ibrutinib show limitations, including resistance mechanisms.

Purpose of the Study:

  • To identify FDA-approved compounds that can be repurposed for DLBCL treatment.
  • To evaluate the efficacy of dasatinib, a multikinase inhibitor, in DLBCL models.
  • To investigate mechanisms of dasatinib resistance and identify potential synergistic therapies.

Main Methods:

  • Screened a library of FDA-approved drugs and targeted compounds against 9 DLBCL cell lines.
  • Validated findings on a panel of 32 genetically characterized DLBCL cell lines and in vivo xenografts.
  • Assessed dasatinib activity, resistance mechanisms (PI3K pathway activation, PTEN loss), and synergistic effects with mTORC2 inhibition.

Main Results:

  • Dasatinib demonstrated efficacy in 50% of DLBCL cell lines and in vivo xenografts, outperforming ibrutinib and overcoming ibrutinib resistance.
  • Dasatinib resistance was associated with PI3K pathway activation and PTEN loss.
  • Inhibition of PI3K via mTORC2 blockade synergized with dasatinib, abolishing resistance both in vitro and in vivo.

Conclusions:

  • Drug repurposing is a viable strategy for identifying new DLBCL treatments.
  • Dasatinib shows significant potential for clinical development in DLBCL and other lymphomas.
  • Targeting the PI3K pathway concurrently with dasatinib can overcome treatment resistance.