Int J Med Sci
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Background: Combination chemotherapy plays an important role in the clinical therapy of non-small cell lung cancer (NSCLC). However, the pharmacokinetic differences between drugs are an insurmountable barrier in traditional treatment. For the synergistic therapy of NSCLC, synergistic nanoparticles (EDS NPs) loaded with both an EGFR inhibitor and doxorubicin (DOX) were designed and prepared. ⋯ The in vivo distribution showed that EDS NPs could enhance accumulation in tumors and decrease nonspecific accumulation in normal organs. EDS NPs significantly promoted the in vivo synergistic effects of icotinib and DOX in the mouse model. Conclusions: The study suggests that EDS NPs possess noteworthy potential for development as therapeutics for NSCLC clinical chemotherapy.
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Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract characterized by inflammation. Although IBD is usually treated with anti-inflammatory agents, most of these treatments have limited efficacy. Propolis is a viscous mixture that honeybees produce by mixing saliva and honeycomb with exudate gathered from tree buds, sap flows, or other botanical sources. ⋯ Furthermore, Korean propolis induced the reduction of the inflammatory cytokine KC, infiltration of immune cells, and colonic hyperplasia in mice with DSS-induced colitis. The Korean propolis also decreased the loss of goblet cells and antibody-reactivity to inflammatory markers in the colons of mice administered DSS. These results demonstrate for the first time that Korean propolis has an ameliorative effect on DSS-induced colonic inflammation in BALB/c mice.
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Confocal Raman microspectral imaging was adopted to elucidate the cellular drug responses of osteosarcoma cells (OC) to N-[N-(3, 5-difluorophenyl acetyl)-L-alanyl]-sphenylglycine butyl ester (DAPT), a γ-secretase inhibitor, by identifying the drug induced subcellular compositional and structural changes. Methods: Spectral information were acquired from cultured osteosarcoma cells treated with 0 (Untreated Group, UT), 10 (10 μM DAPT treated, 10T), 20 μM (20 μM DAPT treated, 20T) DAPT for 24 hours. A one-way ANOVA and Tukey's honest significant difference (HSD) post hoc multiple test were sequentially applied to address spectral features among three groups. ⋯ In an addition, DAPT-induced nuclear fragmentation and apoptosis was depicted by the univariate Raman image of major cellular components (nucleic acids, proteins and lipids). Conclusions: The achieved Raman spectral and imaging results illustrated detailed DAPT-induced subcellular compositional and structural variations as a function of drug dose. Such observations can not only explain drug therapeutic mechanisms of OC DAPT treatment, and also provide new insights for accessing the medicine curative efficacy and predicting prognosis.
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Observational Study
Platelet lysates in Hepatocellular Carcinoma patients after radiofrequency ablation facilitate tumor proliferation, invasion and vasculogenic mimicry.
Background: Platelets play important roles in tumorigenesis, angiogenesis and metastatic dissemination of tumor cells. Radiofrequency ablation (RFA) could increase the circulating tumor cells in patients with primary or metastatic lung tumors. Whether platelet lysates in hepatocellular carcinoma (HCC) after RFA promote tumor progression has not been elaborated. ⋯ Platelet lysates after RFA significantly increased the expression of p-Akt, p-Smad3 and snail, and decreased the expression of E-cadherin compared with those before RFA in Hep3B and HCCLM3 cells. Hep3B-Luc2-tdT cells incubation with platelet lysates from patients after RFA displayed enhanced lung metastasis compared with those before RFA. Conclusions: Platelet lysates from HCC patients after RFA promoted the proliferation, migration, invasion and vasculogenic mimicry of HCC cells, which indicated that RFA in combination with anti-platelet drug may be used to improve the prognosis of HCC.
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Observational Study
Estrogen receptor α/prolactin receptor bilateral crosstalk promotes bromocriptine resistance in prolactinomas.
Prolactinomas are the most common type of functional pituitary adenoma. Although bromocriptine is the preferred first line treatment for prolactinoma, resistance frequently occurs, posing a prominent clinical challenge. Both the prolactin receptor (PRLR) and estrogen receptor α (ERα) serve critical roles in the development and progression of prolactinomas, and whether this interaction between PRLR and ERα contributes to bromocriptine resistance remains to be clarified. ⋯ Furthermore, PRL induced the phosphorylation of ERα via the JAK2-PI3K/Akt-MEK/ERK pathway, while estrogen promoted PRLR upregulation via pERα. ERα inhibition abolished E2-induced PRLR upregulation and PRL-induced ERα phosphorylation, and fulvestrant, an ERα inhibitor, restored pituitary adenoma cell sensitivity to bromocriptine by activating JNK-MEK/ERK-p38 MAPK signaling and cyclin D1 downregulation. Collectively, these data suggest that the interaction between the estrogen/ERα and PRL/PRLR pathways may contribute to bromocriptine resistance, and therefore, that combination treatment with fulvestrant and bromocriptine (as opposed to either drug alone) may exert potent antitumor effects on bromocriptine-resistant prolactinomas.