ABSTRACT
Objective:To investigate the effects of modified Sijunzi Decoction on myelosuppression in moderate- and advanced-stage lung cancer patients with Qi and Yin deficiency and analyze the underlying mechanism. Methods:A total of 100 moderate- and advanced-stage lung cancer patients with Qi and Yin deficiency who received treatment in Lishui Hospital of Traditional Chinese Medicine, China were included in this study. They were randomly assigned to receive chemotherapy with paclitaxel combined with cisplatin (control group, n = 50) or treatment with modified Sijunzi Decoction based on chemotherapy with paclitaxel combined with cisplatin (observation group, n = 50). Myelosuppression, traditional Chinese medicine symptom score, cellular immune function, serum levels of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor, and the dosage of recombinant human granulocyte-colony stimulating factor. Results:After treatment, the incidence of leucopenia, thrombocytopenia, hemoglobinopenia and neutropenia in the observation group were 60% (30/50), 18% (9/50), 18% (9/50) and 62% (31/50), respectively, which were significantly lower than those in the control group [90% (45/50), 30% (15/50), 32% (16/50) and 92% (46/50), χ2 = 6.979, 7.025, 6.534, 6.134, all P < 0.001]. The complete remission rate in the observation group was significantly higher than that in the control group [30% (15/50) vs. 8% (4/50), χ2 = 9.018, P < 0.001]. The traditional Chinese medicine symptom score in the observation group was significantly lower than that in the control group ( t = 6.982, P < 0.05). CD 8+, CD 4+ and CD 3+ levels in the observation group were (25.16 ± 2.87)%, (38.76 ± 4.16)%, (48.83 ± 5.61)%, respectively, and they were (28. 89 ± 4.02)%, (34.10 ± 4.59)%, (41.12 ± 77)%, respectively in the control group. There were significant differences in CD 8+, CD 4+ and CD 3+ levels between the observation and control groups ( t = 6.392, 6.235, 5.983, all P < 0.05). The dosage of recombinant human granulocyte-colony stimulating factor in the observation group was significantly lower than that in the control group [(2 567.34 ± 308.25) μg vs. (3 917.82 ± 411.67) μg, t = 11.258, P < 0.05]. Serum levels of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor were (25.53 ± 7.86) ng/L and (278.34 ± 28.74) ng/L, which were significantly higher than those in the control group [(21.30 ± 3.12) ng/L, (204.17 ± 11.98) ng/L, t = 9.136, 8.856, both P < 0.05]. Conclusion:Modified Sijunzi Decoction for the treatment of moderate- and advanced-stage lung cancer patients with Qi and Yin deficiency can decrease the incidence of myelosuppression possibly through increasing serum levels of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor and improving the immune function.
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable malignancy, with an only 6% 5-year relative survival rate. The dismal therapeutic effect is attributed to the chemotherapy resistance and unique pathophysiology with abundant inflammatory cytokines and abnormal hyperplasia of extracellular matrix (ECM). Based on the theory that bone marrow mesenchymal stem cells (BM-MSCs) can influence the tumorous microenvironment and malignant growth of PDAC, we employed exosomes (Exos) derived from BM-MSCs as PDAC-homing vehicles to surpass the restrictions of pathological ECM and increase the accumulation of therapeutics in tumor site. To overcome chemoresistance of PDAC, paclitaxel (PTX) and gemcitabine monophosphate (GEMP)-an intermediate product of gemcitabine metabolism-were loaded in/on the purified Exos. In this work, the Exo delivery platform showed superiorities in homing and penetrating abilities, which were performed on tumor spheroids and PDAC orthotopic models. Meanwhile, the favorable anti-tumor efficacy and , plus relatively mild systemic toxicity, was found. Loading GEMP and PTX, benefitting from the naturally PDAC selectivity, the Exo platform we constructed performs combined functions on excellent penetrating, anti-matrix and overcoming chemoresistance (Scheme 1). Worth expectantly, the Exo platform may provide a prospective approach for targeted therapies of PDAC.
ABSTRACT
Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for them. The purpose of this work is to construct a self-assembled glutathione (GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription (RCT) method. GSH-responsive cationic polymer polyethyleneimine (pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid (DHA), a targeting molecule, which is a substrate of glucose transporter 1 (GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.
ABSTRACT
The blood-brain barrier (BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme (GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel (PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles (NPs). Here we characterize PTX-loaded human serum albumin (HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P (SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content (7.89%) and entrapment efficiency (85.7%) with a spherical structure (about 150 nm) and zeta potential of -12.0 mV. The drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells (BCECs) and U87 cells was greatly improved. The low IC, prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.
ABSTRACT
Spurred by significant progress in materials chemistry and drug delivery, charge-reversal nanocarriers are being developed to deliver anticancer formulations in spatial-, temporal- and dosage-controlled approaches. Charge-reversal nanoparticles can release their drug payload in response to specific stimuli that alter the charge on their surface. They can elude clearance from the circulation and be activated by protonation, enzymatic cleavage, or a molecular conformational change. In this review, we discuss the physiological basis for, and recent advances in the design of charge-reversal nanoparticles that are able to control drug biodistribution in response to specific stimuli, endogenous factors (changes in pH, redox gradients, or enzyme concentration) or exogenous factors (light or thermos-stimulation).