Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0849640 (skin damage)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For the local irritation caused by Doxorubicin hydrochloride (DXR) which have leaked to the subcutis from the vein, the usefulness of the model using the auricular subcutis of rabbits was examined. DXR was administered to the subcutis in the ear auricle, abdominal region and dorsal region, and the local irritation reactions induced were evaluated according to the Draize criteria, by comparison of the damaged area and by the histopathological method. Macroscopic formations of erythema, edema and eschar were observed in the auricular subcutis, but there were no changes in the abdominal or dorsal subcutis. Histopathological examination showed changes such as edema, hemorrhage and necrosis at all administration sites and the changes were most severe in the auricular subcutis among the 3 regions. The reactions in the ear auricle observed were closest to the skin damage noted in humans by administration of DXR. In order to find out why the degree of local damage is different in these 3 regions, Evans blue was administered to these regions to compare its diffusibility in these regions. The diffusibility of Evans blue was lowest in the ear auricle. It is estimated that the difference in the local damage induced by DXR in these regions might be due to the difference in the retention time of DXR in the subcutis. Therefore, the evaluation for local irritation using the auricular subcutis model in rabbits is considered to be useful for estimation of skin damage caused by leakage of DXR to the subcutis.
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PMID:Useful method for evaluation of local irritation using auricular subcutis of rabbits. 2229 24

Multidrug resistance (MDR) of cancers that results from overexpression of a P-glycoprotein (P-gp) transporter mainly causes chemotherapy (CT) failure and hinders clinical transitions of current polypeptide nanomedicines. Herein, a novel polypeptide nanocomposite PNOC-PDA that integrates heat-sensitive NO gas delivery and photothermal conversion attributes can overcome MDR and maximize CT; meanwhile the optimized CT and intracellular high-concentration NO gas can assist a mild photothermal therapy (PTT) to eradicate cancer cells. The triple therapies produced a superior and synergistic effect on MDR-reversal and killing MCF-7/ADR in vitro, and the P-gp expression level was downregulated to 46%, as confirmed by means of MTT, Western blot, flow cytometry, and confocal laser scanning microscopy. Significantly, by using one intravenous injection of PNOC-PDA/DOX and a single near-infrared irradiation, the triple therapies of mild PTT, NO gas therapy, and CT achieved complete MCF-7/ADR tumor ablation without skin damage, scarring, and tumor recurrence within 30 days. This work provides a versatile method for the fabrication of NIR-responsive polypeptide nanocomposite with intrinsic photothermal conversion and NO-releasing attributes, opening up a new avenue for reversing MDR in tumors.
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PMID:NIR-Responsive Polypeptide Nanocomposite Generates NO Gas, Mild Photothermia, and Chemotherapy to Reverse Multidrug-Resistant Cancer. 3119 53

Combating multidrug resistance (MDR) of tumors is still challenging for clinical chemotherapy, cocktail chemotherapy (CCT), and currently widely-studied nanodrug-based treatments. Inspired by different MDR-overcoming and antitumor mechanisms of CCT and photothermal therapy (PT), a dual drug-paired polyprodrug nanoparticle (PDCN25-CDDP) was constructed to achieve the combination therapy PT-CCT for reversing MDR and combating multidrug resistant cancers. The PT-CCT treatment can greatly downregulate the P-gp expression level and achieve utmost MDR-reversal and antitumor efficacy by both a cocktail effect of CCT and a synergistic effect of CCT with PT; meanwhile, PT can inhibit the expression of heat shock protein 90 and enhance the thermosensitivity of cancer cells. Upon NIR irradiation, PDCN25-CDDPin vivo produced a selective tumor accumulation effect and relatively deep tumor penetration, as evidenced by fluorescent and photoacoustic imaging and CLSM. The mild PT-CCT treatment completely eradicated MCF-7/ADR and OVCAR-3/DDP tumors without skin damage or tumor recurrence for 30 days, exhibiting synergistic MDR-reversal and superior antitumor efficacy in vivo. Importantly, this work provides an innovative strategy for reversing MDR and combating DOX-resistant breast and CDDP-resistant ovarian cancers.
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PMID:Dual drug-paired polyprodrug nanotheranostics reverse multidrug resistant cancers via mild photothermal-cocktail chemotherapy. 3141 Dec 35