Cellular senescence contributes to tumor regression through both cell autonomous and non-autonomous mechanisms. Drugs inducing cancer cell senescence and modulating senescence-associated secretory phenotype (SASP) render advantage to the cancer treatment. Breast cancer remains the second most cause of female cancer mortality, among which triple-negative breast cancer (TNBC) has a more aggressive clinical course. Our study showed that in TNBC cell lines including MDA-MB-231 and 4T1 cells, moderate concentrations of wogonin (5, 7-dihydroxy-8-methoxy-2-phenyl-4h-1-benzopyran-4-one) (50-100 μM) not only induced permanent proliferation inhibition, but also increased P16 expression, β-galactosidase activity, senescence-associated heterochromatin foci and SASP, which are the typical characteristics of cellular senescence. Moreover, results showed that wogonin-induced senescence was partially attributed to the reactive oxygen species (ROS) accumulation upon wogonin treatment in MDA-MB-231 cells, since elimination of ROS by N-acetylcysteine (NAC) was able to repress wogonin-induced β-galactosidase activity. Mechanistically, wogonin reduced the expression of TXNRD2, an important antioxidant enzyme in controlling the levels of cellular ROS, by altering the histone acetylation at its regulatory region. In addition, senescent MDA-MB-231 cells induced by wogonin exhibited activated NF-κB and suppressed STAT3, which were recognized as regulators of SASP. SASP from these senescent cells suppressed tumor cell growth, promoted macrophage M1 polarization in vitro and increased immune cell infiltration in xenografted tumors in vivo. These results reveal another mechanism for the anti-breast cancer activity of wogonin by inducing cellular senescence, which suppresses tumor progression both autonomously and non-autonomously.
Bromodomain-containing 4 (BRD4), a member of Bromo and Extra-Terminal (BET) family, recognizes acetylated histones and is of importance in transcription, replication, and DNA repair. It also binds non-histone proteins, DNA and RNA, contributing to development, tissue growth, and various physiological processes. Additionally, BRD4 has been implicated in driving diverse diseases, ranging from cancer, viral infection, inflammation to neurological disorders. Inhibiting its functions with BET inhibitors (BETis) suppresses the progression of several types of cancer, creating an impetus for translating these chemicals to the clinic. The diverse roles of BRD4 are largely dependent on its interaction partners in different contexts. In this review we discuss the molecular mechanisms of BRD4 with its interacting partners in physiology and pathology. Current development of BETis is also summarized. Further understanding the functions of BRD4 and its partners will facilitate resolving the liabilities of present BETis and accelerate their clinical translation.
With the use of low-dose CT for early screening of lung cancer, more and more early lung cancers are found. At the same time, patients with small lung nodules have also increased, it is a great challenge for surgeons to resect pulmonary nodules with small volume, deep position and no solid components under video-assisted thoracoscopic surgery. Many studies have reported preoperative and intraoperative methods for localizing lung nodules before minimally invasive resection. Methods for preoperative localization include CT-guided hook-wire positioning, coil positioning, or dye injection and radionuclide location Methods for intraoperative localization include intraoperative ultrasound localization and tactile pressure-sensing localization. After the localization of pulmonary nodules under the guidance of CT patients need to restrict their activities; otherwise, it is easy for the nodules to move, causing the operation to fail, and may also cause complications such as pneumothorax, puncture site pain, and pulmonary parenchymal bleeding. In the past, we injected melamine dye under the guidance of electromagnetic navigation bronchoscope to locate lung nodules. The purpose of this case is introducing a new method for accurately localizing and resecting pulmonary nodules by injecting indocyanine green (ICG) under the guidance of electromagnetic navigation bronchoscope and the resection of small pulmonary nodules under the fluoroscope.
Alzheimer disease (AD) seriously harms human health and its onset is insidious. Therefore, it is of great significance to find out the pathogenesis of AD disease for improving the prevention and treatment effect of the disease. The study drew attention to the influence of E2F-1/NF-κB/GSK-3β signaling pathway on cognitive dysfunction of Alzheimer rats. 60 specific pathogen-free (SPF) SD rats were selected as research subjects. The, the AD model was created by injecting Aβ1-42 into hippocampus CA1 region of AD rats using a microscopic syringe. Besides, Morris water maze test and Western blot were performed to detect the cognitive function, the levels of destination protein and active oxidation products in the brain of rats. Compared to the Sham group, the escape latency and the distance of the model group significantly increased (
P <
0.05), and the number of times to pass the target quadrant was significantly reduced (
P <
0.05); the expression levels of E2F-1 and NF-κB protein in the hippocampus and the phosphorylation levels of Tau231, Tau262, Tau396, Tau404 and T216-GSK-3β protein of the model group were significantly increased (
P <
0.05); the ROS/RNS value in the hippocampus of the model group significantly increased (
P <
0.05). AD model rats exhibit obvious cognitive dysfunction, which is associated with the activation of E2F-1/NF-κB/GSK-3β signaling pathway and the heightened Tau protein phosphorylation level.
Background Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) is an imaging method used to analyze oxygenation status of the tumor. Purpose To investigate the feasibility of BOLD-MRI in evaluating the efficacy of advanced cervical cancer combined with radiotherapy and chemotherapy. Material and Methods This prospective study included 85 patients with advanced cervical cancer who received BOLD-MRI examination before and after concurrent chemoradiotherapy from October 2020 to December 2021. To investigate the changes of baseline R2* values and △R2* values of cervical cancers before and after treatment. Results 29 cases were complete response, 34 cases were partial response, and 22 cases showed progression. The baseline R2* values of the tumors were lower than that of the normal cervical muscle ( P < 0.0001). After oxygen stimulation, the baseline R2* values of the tumors decreased ( P = 0.012). After treatment, the baseline R2* values of the tumors increased ( P = 0.007), and the dynamic △R2* values of the tumors decreased ( P = 0.025). The baseline R2* value of the complete response was the highest ( P = 0.000), the dynamic △R2* value of the complete response was the lowest ( P = 0.017). Conclusion BOLD-MRI can evaluate the efficacy of concurrent chemoradiotherapy for advanced cervical cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.