Disease Information

General Information of the Disease (ID: DIS00330)

• Name: Keloid/hypertrophic scars
• ICD: ICD-11: EE60

Type(s) of Resistant Mechanism of This Disease

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 4 drug(s) in total

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [1]

• Resistant Disease: Hypertrophic scar [ICD-11: EE60.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Etoposide
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Hypertrophic scar tissue isolates; .
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Fibroblasts derived from hypertrophic scar and normal skin tissues were first compared for their resistance to verapamil and etoposide phosphate. Scar fibroblasts showed stronger resistance to both verapamil and etoposide than normal fibroblasts, also scar fibroblasts expressed more P-glycoprotein and MRP1 than normal fibroblasts.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Resistant Disease: Hypertrophic scar [ICD-11: EE60.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Etoposide
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Hypertrophic scar tissue isolates; .
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Fibroblasts derived from hypertrophic scar and normal skin tissues were first compared for their resistance to verapamil and etoposide phosphate. Scar fibroblasts showed stronger resistance to both verapamil and etoposide than normal fibroblasts, also scar fibroblasts expressed more P-glycoprotein and MRP1 than normal fibroblasts.

Mitoxantrone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Resistant Disease: Keloid [ICD-11: EE60.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Mitoxantrone
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell growth; Activation; hsa05200
• In Vitro Model: Keloid fibroblasts; .
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MDR-1-positive keloid cells exhibited roundness as opposed to the usual spindle shape. Contrarily, MDR-1-positive cells in normal skin remained spindle shaped. Such a phenomenon suggests that MDR-1 positive keloid cells represent a subpopulation important in keloid pathogenesis. MDR-1 (also known as ABCB1 or P-glycoprotein) is one of the best characterized membrane transporters.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Resistant Disease: Keloid [ICD-11: EE60.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Mitoxantrone
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell growth; Activation; hsa05200
• In Vitro Model: Keloid fibroblasts; .
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MDR-1-positive keloid cells exhibited roundness as opposed to the usual spindle shape. Contrarily, MDR-1-positive cells in normal skin remained spindle shaped. Such a phenomenon suggests that MDR-1 positive keloid cells represent a subpopulation important in keloid pathogenesis. MDR-1 (also known as ABCB1 or P-glycoprotein) is one of the best characterized membrane transporters.

Verapamil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [1]

• Resistant Disease: Hypertrophic scar [ICD-11: EE60.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Verapamil
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Hypertrophic scar tissue isolates; .
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Fibroblasts derived from hypertrophic scar and normal skin tissues were first compared for their resistance to verapamil and etoposide phosphate. Scar fibroblasts showed stronger resistance to both verapamil and etoposide than normal fibroblasts, also scar fibroblasts expressed more P-glycoprotein and MRP1 than normal fibroblasts.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Resistant Disease: Hypertrophic scar [ICD-11: EE60.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Verapamil
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Hypertrophic scar tissue isolates; .
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Fibroblasts derived from hypertrophic scar and normal skin tissues were first compared for their resistance to verapamil and etoposide phosphate. Scar fibroblasts showed stronger resistance to both verapamil and etoposide than normal fibroblasts, also scar fibroblasts expressed more P-glycoprotein and MRP1 than normal fibroblasts.

Vincristine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Resistant Disease: Keloid [ICD-11: EE60.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Vincristine
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell growth; Activation; hsa05200
• In Vitro Model: Keloid fibroblasts; .
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MDR-1-positive keloid cells exhibited roundness as opposed to the usual spindle shape. Contrarily, MDR-1-positive cells in normal skin remained spindle shaped. Such a phenomenon suggests that MDR-1 positive keloid cells represent a subpopulation important in keloid pathogenesis. MDR-1 (also known as ABCB1 or P-glycoprotein) is one of the best characterized membrane transporters.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Resistant Disease: Keloid [ICD-11: EE60.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Vincristine
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell growth; Activation; hsa05200
• In Vitro Model: Keloid fibroblasts; .
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MDR-1-positive keloid cells exhibited roundness as opposed to the usual spindle shape. Contrarily, MDR-1-positive cells in normal skin remained spindle shaped. Such a phenomenon suggests that MDR-1 positive keloid cells represent a subpopulation important in keloid pathogenesis. MDR-1 (also known as ABCB1 or P-glycoprotein) is one of the best characterized membrane transporters.

References

• Ref 1: Disruption of the association between drug transporter and actin cytoskeleton abolishes drug resistance in hypertrophic scar .Oncotarget. 2017 Jan 10;8(2):2617-2627. doi: 10.18632/oncotarget.13734. 10.18632/oncotarget.13734
• Ref 2: Enhanced expression of membrane transporter and drug resistance in keloid fibroblasts .Hum Pathol. 2012 Nov;43(11):2024-32. doi: 10.1016/j.humpath.2011.12.026. Epub 2012 May 21. 10.1016/j.humpath.2011.12.026