Int J Med Sci
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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.
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Cancer vasculature is immature, disorganized and hyperpermeable and can serve as a target for anti-cancer therapies. Vascular disrupting agents (VDAs) are tubulin protein binding and depolymerizing agents that induce rapid tumoral vascular shutdown and subsequent cancer necrosis. ⋯ Nearly complete tumor necrosis was achieved by only a single arterial dose of C118P at 5 mg/kg, which was documented in a representative case by in vivo digital subtraction arteriogram (DSA) and magnetic resonance imaging (MRI), and further confirmed by ex vivo microangiogram and histopathology. This convincing and promising preliminary outcome would warrant further comprehensive studies to explore the potentials of VDAs by transarterial administration either in mono-drug or in combination for management of solid cancers.
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Diabetes mellitus (DM) is a chronic disease found worldwide. Notably, BKS. Cg- Dock7m+/+ Leprdb/JNarl mice are useful animal models for studying type 2 diabetes mellitus (T2DM). ⋯ Cg- Dock7m +/+ Leprdb/JNarl in the mouse model by demonstrating a significant increase in gene and protein expression in T2DM (+Leprdb/+Leprdb) mouse liver when compared to control (+Dock7m/+Dock7m) mouse liver. We also observed that CSNK2A1 protein level in the serum of T2DM patient group was higher than that of the control group, although the data was not statistically significant. Based on our findings, we can now understand the role of CSNK2A1 gene upregulation when encountering T2DM pathologies.
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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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Background and aim: We established a porcine model of one-lung flooding (OLF) that can be used for research on the use of ultrasound for lung tumour detection, ultrasound-guided transthoracic needle biopsy, and tumour ablation. However, OLF requires one-lung ventilation (OLV) and eliminates the recruitment strategies of the nonventilated lung. During thoracic surgery, OLV alone can be associated with hypoxia, hypercapnia, and right ventricular overload. ⋯ No clinically relevant deterioration of haemodynamics or gas exchange occurred during or after OLF. Due to the circulatory arrest in the flooded lung, the right-to-left shunt volume in the nonventilated lung was minimized. Survival experiments are necessary to further assess the utility of this method.