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Carrier-Mediated Transport01:06

Carrier-Mediated Transport

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Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
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Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

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In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
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Membrane Transporters01:31

Membrane Transporters

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Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
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Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

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Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
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The Significance of Membrane Transport01:44

The Significance of Membrane Transport

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The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
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Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
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Related Experiment Video

Updated: Sep 13, 2025

Author Spotlight: Investigating Liver Cancer Pathogenesis Using Patient-Derived Organoids
07:25

Author Spotlight: Investigating Liver Cancer Pathogenesis Using Patient-Derived Organoids

Published on: August 18, 2023

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Monocarboxylate Transporter-1 Is Dispensable for Hepatocellular Carcinoma Development.

Shaimaa A Gad1,2,3, Bryan Bridgeman1,2, Kyle Boedeker1,2

  • 1Departments of Surgery, Pathology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.

Molecular Carcinogenesis
|July 31, 2025
PubMed
Summary

Monocarboxylate transporter-1 (MCT1) is not essential for liver cancer development. Knocking out MCT1 in liver cells did not prevent or reduce hepatocellular carcinoma (HCC) growth or its associated symptoms in mouse models.

Keywords:
dispensablehepatocellular carcinomametabolismmonocarboxylate transporter 1

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Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolism

Background:

  • Hepatocellular carcinoma (HCC) is a deadly liver cancer requiring understanding of its molecular drivers.
  • Monocarboxylate transporter-1 (MCT1) regulates cell metabolism and is upregulated in HCC, but its precise role needs clarification in vivo.
  • Previous studies showed MCT1 inhibition reduced tumor growth in xenografts, necessitating investigation in immune-competent models.

Purpose of the Study:

  • To investigate the role of liver-specific Monocarboxylate transporter-1 (MCT1) in hepatocellular carcinoma (HCC) development using an immune-competent mouse model.
  • To determine if deleting MCT1 in liver cells affects HCC progression, tumor characteristics, and associated pathological features.

Main Methods:

  • Established liver-specific MCT1 knockout mice.
  • Induced HCC using the DEN/CCl4 model in wild-type and MCT1 knockout mice.
  • Assessed tumor size, count, proliferation (Ki67), fibrosis (collagen A1), and inflammation (myeloperoxidase) via immunohistochemistry.

Main Results:

  • Liver-specific deletion of MCT1 did not alter liver cell morphology, proliferation, or apoptosis.
  • MCT1 knockout did not significantly reduce the size or number of DEN/CCl4-induced HCC tumors.
  • MCT1 knockout failed to inhibit proliferation, fibrosis, or inflammation in the HCC model.

Conclusions:

  • Monocarboxylate transporter-1 (MCT1) is dispensable for the development of hepatocellular carcinoma (HCC) in this model.
  • MCT1 deletion is insufficient to mitigate the progression or pathological features of DEN/CCl4-induced HCC.
  • Targeting MCT1 may not be a viable strategy for treating HCC, warranting further research into other metabolic pathways.