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901.
Ligands for peroxisome proliferator-activated receptorγ and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice 下载免费PDF全文
Elena Elstner Carsten Müller Kozo Koshizuka Elizabeth A. Williamson Dorothy Park Hiroya Asou Peter Shintaku Jonathan W. Said David Heber H. Phillip Koeffler 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(15):8806-8811
Induction of differentiation and apoptosis in cancer cells through ligands of nuclear hormone receptors (NHRs) is a novel and promising approach to cancer therapy. All-trans-retinoic acid (ATRA), an RA receptor-specific NHR ligand, is now used for selective cancers. The NHR, peroxisome proliferator-activated receptor γ (PPARγ) is expressed in breast cancer cells. Activation of PPARγ through a synthetic ligand, troglitazone (TGZ), and other PPARγ-activators cause inhibition of proliferation and lipid accumulation in cultured breast cancer cells. TGZ (10−5 M, 4 days) reversibly inhibits clonal growth of MCF7 breast cancer cells and the combination of TGZ (10−5 M) and ATRA (10−6 M, 4 days) synergistically and irreversibly inhibits growth and induces apoptosis of MCF7 cells, associated with a dramatic decrease of their bcl-2 protein levels. Similar effects are noted with in vitro cultured breast cancer tissues from patients, but not with normal breast epithelial cells. The observed apoptosis mediated by TGZ and ATRA may be related to the striking down-regulation of bcl-2, because forced over-expression of bcl-2 in MCF7 cells cultured with TGZ and ATRA blocks their cell death. TGZ significantly inhibits MCF7 tumor growth in triple immunodeficient mice. Combined administration of TGZ and ATRA causes prominent apoptosis and fibrosis of these tumors without toxic effects on the mice. Taken together, this combination may provide a novel, nontoxic and selective therapy for human breast cancers. 相似文献
902.
Papaya (Carica papaya) is widely cultivated in many tropical regions of the world. With an estimated 30–50% cull rate, there is a large amount of off-grade papaya produced. Here, we report very low-cost processing of culled papaya fruit waste, without needing any complex mechanized operations, to yield several products, including seed oil, sugar-rich puree, detoxified/defatted seed meal, and crude myrosinase and glucosinolates with antimicrobial and biofumigation applications. We then demonstrated that both puree and seed oil can serve as effective carbon substrates for cultivation of the oleaginous yeast Yarrowia lipolytica to produce single-cell proteins and high-value recombinant protein products. To use papaya seed oil for culturing Y. lipolytica, the concentration of the inhibitory substance benzyl isothiocyanate (BITC) in the oil needs to be minimized. If the culled fruits (and hence seeds) were stored frozen prior to drying, a very high level (>30 mM) of BITC was detected in the oil extracted from the dried seeds. However, if the seeds were not frozen prior to drying, oil from dried papaya seeds contained almost no BITC, and could support vigorous growth of Y. lipolytica, with efficient production of a functional nanobody fusion protein at a level similar to that achieved using olive oil. By using both juice and seed lipid, rather than juice alone, Y. lipolytica biomass produced per unit papaya more than doubled. As Y. lipolytica is amenable to genetic manipulation, and is known as a proficient cell factory with many industrial applications, the papaya waste valorization technology could potentially be extended to produce additional useful products such as biofuel and oleochemicals from Y. lipolytica.Seed oil from papaya waste was validated as a novel carbon substrate for Yarrowia lipolytica to produce high-value products. 相似文献
903.
904.
Joo-Hui Han Yohan Kim Sang-Hyuk Jung Jung-Jin Lee Hyun-Soo Park Gyu-Yong Song Nguyen Manh Cuong Young Ho Kim Chang-Seon Myung 《The Korean journal of physiology & pharmacology》2015,19(5):421-426
The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through G0/G1 to S phase of the cell cycle, as measured by [3H]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at G0/G1 phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis. 相似文献
905.
Huan-Jun Lu Mei-Han Li Mei-Zhi Li Sang Eon Park Min Sun Kim Yuan-Zhe Jin Byung Rim Park 《The Korean journal of physiology & pharmacology》2015,19(5):427-434
Significant evidence supports the role of the vestibular system in the regulation of blood pressure during postural movements. In the present study, the role of the vestibulo-spino-adrenal (VSA) axis in the modulation of blood pressure via the vestibulosympathetic reflex was clarified by immunohistochemical and enzyme immunoassay methods in conscious rats with sinoaortic denervation. Expression of c-Fos protein in the intermediolateral cell column of the middle thoracic spinal regions and blood epinephrine levels were investigated, following microinjection of glutamate receptor agonists or antagonists into the medial vestibular nucleus (MVN) and/or sodium nitroprusside (SNP)-induced hypotension. Both microinjection of glutamate receptor agonists (NMDA and AMPA) into the MVN or rostral ventrolateral medullary nucleus (RVLM) and SNP-induced hypotension led to increased number of c-Fos positive neurons in the intermediolateral cell column of the middle thoracic spinal regions and increased blood epinephrine levels. Pretreatment with microinjection of glutamate receptor antagonists (MK-801 and CNQX) into the MVN or RVLM prevented the increased number of c-Fos positive neurons resulting from SNP-induced hypotension, and reversed the increased blood epinephrine levels. These results indicate that the VSA axis may be a key component of the pathway used by the vestibulosympathetic reflex to maintain blood pressure during postural movements. 相似文献
906.
Ju-Hyung Park Geun Mook Park Jin-Kyung Kim 《The Korean journal of physiology & pharmacology》2015,19(4):335-340
Here, we investigated the role of zerumbone, a natural cyclic sesquiterpene of Zingiber zerumbet Smith, on angiogenesis using human umbilical vein endothelial cells (HUVECs). Zerumbone inhibited HUVECs proliferation, migration and tubule formation, as well as angiogenic activity by rat aorta explants. In particular, zerumbone inhibited phosphorylation of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1, which are key regulators of endothelial cell function and angiogenesis. In vivo matrigel plug assay in mice demonstrated significant decrease in vascularization and hemoglobin content in the plugs from zerumbone-treated mice, compared with control mice. Overall, these results suggest that zerumbone inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects. 相似文献
907.
Chronic inflammation has been proposed as one of the main molecular mechanisms of aging and age-related diseases. Although evidence in humans is limited, short-term calorie restriction (CR) has been shown to have anti-inflammatory effects in aged experimental animals. We reported on the long-term treatment of daumone, a synthetic pheromone secreted by Caenorhabditis elegans in an energy deficient environment, extends the life-span and attenuates liver injury in aged mice. The present study examined whether late onset short-term treatment of daumone exerts anti-inflammatory effects in the livers of aged mice. Daumone was administered orally at doses of 2 or 20 mg/kg/day for 5 weeks to 24-month-old male C57BL/6J mice. Increased liver macrophage infiltration and gene expression of proinflammatory cytokines in aged mice were significantly attenuated by daumone treatment, suggesting that short-term oral administration of daumone may have hepatoprotective effects. Daumone also dose-dependently suppressed tumor necrosis factor-α (TNF-α)-induced nuclear factor-κB (NF-κB) phosphorylation in HepG2 cells. The present data demonstrated that short-term treatment of daumone has anti-inflammatory effects in aged mouse livers possibly through suppression of NF-κB signaling and suggest that daumone may become a lead compound targeting aging and age-associated diseases. 相似文献
908.
Yoon Hee Chung Young Joo Lee Ho Sung Lee Su Jin Chung Cheol Hee Lim Keon Woong Oh Uy Dong Sohn Eon Sub Park Ji Hoon Jeong 《The Korean journal of physiology & pharmacology》2015,19(1):15-20
This study was aimed to observe that extremely low frequency magnetic field (ELF-MF) may be relevant to changes of major neurotransmitters in rat brain. After the exposure to ELF-MF (60 Hz, 2.0 mT) for 2 or 5 days, we measured the levels of biogenic amines and their metabolites, amino acid neurotransmitters and nitric oxide (NO) in the cortex, striatum, thalamus, cerebellum and hippocampus. The exposure of ELF-MF for 2 or 5 days produced significant differences in norepinephrine and vanillyl mandelic acid in the striatum, thalamus, cerebellum and hippocampus. Significant increases in the levels of serotonin and 5-hydroxyindoleacetic acid were also observed in the striatum, thalamus or hippocampus. ELF-MF significantly increased the concentration of dopamine in the thalamus. ELF-MF tended to increase the levels of amino acid neurotransmitters such as glutamine, glycine and γ -aminobutyric acid in the striatum and thalamus, whereas it decreased the levels in the cortex, cerebellum and hippocampus. ELF-MF significantly increased NO concentration in the striatum, thalamus and hippocampus. The present study has demonstrated that exposure to ELF-MFs may evoke the changes in the levels of biogenic amines, amino acid and NO in the brain although the extent and property vary with the brain areas. However, the mechanisms remain further to be characterized. 相似文献
909.
Introduction:Intraductal papillary mucinous neoplasm of the biliary tract (IPNB) is a rare, low-grade neoplasm limited to the bile duct mucosa. The malignant transformation rate is low, and there have been limited reports of metastasis to other organs. Herein, we presented a rare case of a patient who was diagnosed with IPNB concurrent with invasive adenocarcinoma after surgery and was diagnosed with cardiac metastasis 6 months later.Patient concerns:A 61-year-old male patient presented with abdominal pain to a local clinic. He was diagnosed with intrahepatic cholangiocarcinoma with pancreatitis and transferred to our hospital.Diagnosis:Diagnostic testing (magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, positron emission tomography-computed tomography) revealed a papillary neoplasm and invasive adenocarcinoma with papillary neoplasm in the periampullary lesion.Interventions:Pancreaticoduodenectomy, right hemihepatectomy, and left lateral sectionectomy of the liver were performed. After surgery, we planned gemcitabine-based adjuvant chemotherapy.Outcomes:Upon completion of the sixth gemcitabine chemotherapy cycle, a hyperechoic, oval-shaped mass (1.3 × 2.6 cm) was found on the outer wall of the right atrium. Resection of a cardiac tumor in the right atrium and patch repair were performed.Conclusion:To our knowledge, no other case of cardiac metastasis found during observation after surgery for an IPNB has been described. IPNBs are known to be less aggressive and to have a lower metastasis rate than intraductal papillary mucinous neoplasms; therefore, the number of case reports describing metastasis after surgery is relatively low. Our case suggests that close observation is necessary in patients diagnosed with an IPNB. 相似文献
910.
Eun Jung Jung Ju-Yeon Kim Jae-Myung Kim Han Shin Lee Seung-Jin Kwag Ji-Ho Park Taejin Park Sang-Ho Jeong Chi-Young Jeong Young-Tae Ju Young-Joon Lee Soon-Chang Hong 《Medicine》2021,100(11)
This study evaluated the outcomes and prognostic factors for breast cancer according to initial lymph node (LN) status. Among patients with LN-negative breast cancer, we also focused on the prognostic value of estrogen receptor (ER) status.Medical records were retrospectively reviewed for 715 patients who underwent curative surgery for breast cancer between January 2005 and December 2015 at a single Korean institution. We evaluated factors that were associated with metastasis-free survival (MFS) according to LN status.Among the 715 patients (age: 28–87 years), 458 patients (64.1%) did not have axillary LN metastasis. Relative to patients without LN metastasis, patients with LN metastasis had larger tumor sizes and higher histological grades. Among patients with no LN metastasis, ER positivity was associated with non-significantly poorer MFS than ER negativity (mean survival: 138.90 months vs. 146.99 months, p = .17), and patients with LN-negative ER-positive disease had MFS rates of 91.7% at 5 years and 74.5% at 10 years. Among patients with LN-negative ER-positive disease, a poor prognosis was significantly associated with larger tumor size (≥2 cm, P = .03) and older age (≥50 years, P = .03).These results indicate that the risk of metastasis increases over time for patients with LN-negative ER-positive breast cancer, and especially for older patients or patients with larger tumors. 相似文献