The changes in tumor volume, adverse reactions and survival of patients in the TP group and rAd-p53 + TP group, and the levels of p53, ASPP2, inhibitory member of the ASPP family (iASPP) and P-gp in postoperative tumor tissues in the 3 groups were evaluated.
Despite this achievement, general principles from proposed systems pharmacokinetic modeling for intracellular processing of ADCs indicate potential shortcomings of T-DM1: (i) <i>C</i><sub>max</sub> limited by toxicities; (ii) slow internalization rate; (iii) resistance mechanisms due to defects in intracellular trafficking [loss of lysosomal transporter solute carrier family 46 member 3, (SLC46A3)], and increased expression of drug transporters MDR1 and MRP1; and (iv) lack of payload bystander effects limiting utility in tumors with heterogeneous HER2 expression.
Here, we show that competitive inhibition of MDR1 restored sensitivity to BV in our BV-resistant cell lines by increasing intracellular MMAE levels, and potentiated BV activity in BV-resistant HL tumors in a human xenograft mouse model.
In addition, NO has other multiple synergistic cancer treatment functions, including tumor tissue vasodilatation for drug extravasation promotion, P-glycoprotein (P-gp) downregulation for drug efflux inhibition, and glutathione depletion for cancer cell endogenous antioxidant defense destruction.
In this study, a plasmid DNA which expressed small hairpin RNA of PD-L1 (shPD-L1) was loaded in the ultrasensitive pH triggered charge/size dual-rebound P[(GP)D] nanoparticles (NPs) to silence the PD-L1 gene for reducing the PD-L1/PD-1 interactions between tumors and T cells.
As expected, tumors treated by free doxorubicin hydrochloride (DOX·HCl) showed obvious increase of P-glycoprotein, while for tumors treated by nanocarrier encapsulated doxorubicin, the P-glycoprotein level stayed low as untreated group.
ABCG2/ABCB1 ratios in surgically resected tumor tissue (1.4 ± 0.2) were comparable to previously reported ABCG2/ABCB1 ratios in isolated human micro-vessels (1.3), which suggested that no overexpression of ABCB1 or ABCG2 occurred in the investigated tumors.
Specifically, hydrophilic anticancer irinotecan (Ir) and hydrophobic P-gp protein inhibitor quinine (Qu) are linked by a redox responsive bridge for overcoming MDR of tumors.
[<sup>18</sup>F]AVT-011 is a dual ABCB1/ABCG2 substrate radiotracer that can quantify transporter function at the blood-brain barrier and in ABCB1-expressing tumors, making it potentially suitable for clinical imaging of ABCB1-mediated MDR in tumors.
Due to the high oxygen capacity of such nanoparticles, the hypoxic tumor microenvironment was greatly modulated after these nanoparticles reached the tumor region, and the results revealed that hypoxia-inducible factor α (HIF-1α) was down-regulated and the expression of P-glycoprotein (P-gp) was then reduced, which were in favor of chemotherapy.
Although dietary ellagic acid did not alter the tumor growth inhibition by docetaxel of xenografted 22Rv1 cells, ellagic acid has the potential to interfere with taxane chemotherapy by reducing tubulin polymerization while inhibiting P-glycoprotein drug efflux.
P-glycoprotein (P-gp) is an important determinant of multidrug resistance (MDR) because its overexpression is associated with increased efflux of various established chemotherapy drugs in many clinically resistant and refractory tumors.
Our study demonstrates significant differences in lung tumor detectability on chest radiographs between PGY-1 trainees and pulmonary specialists according to tumor size, extent of GGO, and tumor location.
Three members of ABC transporters superfamily, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and ABCB5 were investigated, whose overexpression in tumors is tightly linked to multidrug resistance.
Furthermore, HDAC1 silencing by Panobinostat and/or lentivirus mediated RNA interference against HDAC1 effectively reduced doxorubicin resistance, resulting in the inhibition of tumor growth in AML bearing mice.
Western blot and polymerase chain reaction analyses showed that inhibition of P-glycoprotein and X-linked inhibitor of apoptosis protein expression may underlie inhibition of tumor resistance mediated by NPs.
As a major clinical tumor chemotherapeutic burden, multidrug resistance (MDR) is often a result of up-regulation of P-glycoprotein (P-gp), which strongly enhances anticancer drug efflux.
Hypermethylation of the analyzed ABCB1 promoter region was significantly correlated with low levels of the ABCB1 transcript in tumors from a subset of patients with breast and ovarian carcinoma prior to chemotherapy but not following treatment.