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941.
JAYNE E. ELLIS MICHAEL A. WYDER LINDA ZHOU ARUN GUPTA HARRY RUDNEY EDNA S. KANESHIRO 《The Journal of eukaryotic microbiology》1996,43(3):165-170
The lipids of purified preparations of Pneumocystis carinii carinii freshly isolated from infected rats were analyzed and compared with those of whole lungs from normal and methylprednisolone-immunosuppressed uninfected rats. In this study, the neutral lipid fraction was examined in detail; the relative concentrations of individual classes making up this fraction were quantified. Of particular interest was the nature of the organism's ubiquinone (coenzyme Q, CoQ) fraction because atovaquone, a hydroxynaphtho-quinone (566C80) analog of ubiquinone, is efficacious in the treatment of P. carinii pneumonia. The ubiquinone concentration in both P. carinii and lung tissues was relatively low compared to that present in rat heart and liver tissues. Two homologs were identified in the organism: CoQ10 was the predominant homolog with lesser amounts of CoQ9 present. In contrast, the lungs of normal and immunosuppressed uninfected rats had CoQ9 and lesser amounts of CoQ8 , but no detectable CoQ10 . Furthermore, radiolabeled mevalonic acid was incorporated in vitro into the ubiquinone fraction of P. carinii indicating that the organism has the de novo branch of the isoprenoid biosynthetic pathway leading to polyprenyl formation. Hence, it was concluded that CoQ10 (if not both CoQ110 and CoQ9 ) in P. carinii as not scavenged from the host but was synthesized by the organism. Although lung tissues contained substantial free fatty acids, the organism was enriched in these lipids. The high concentration of free fatty acids and relatively low level of triglycerides in P. carinii suggest that fatty acids may represent major carbon sources for ATP production by the organism. 相似文献
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943.
Jonathan B Catterall Michael J Gardner Lindsay M.H Jones Graham A Turner 《Glycoconjugate journal》1997,14(5):647-649
Ovarian cancer has the highest mortality rate of any gynaecological malignancy. This is caused by metastatic deposits obstructing
the intestinal tract. Very little is known about the molecules involved in the initial attachment of the metastatic tumour
cells to the peritoneal mesothelial lining. Previously, we showed that many ovarian tumour lines express the adhesion molecule,
CD44, on their cell surface. The major ligand for CD44 is the extracellular matrix glycosaminoglycan, hyaluronic acid (HA).
Because mesothelial cells have a pericellular cost that contains large amounts of HA, it was postulated that the CD44/HA interaction
is an important stage in ovarian cancer spread. However, it was difficult to demonstrate this interaction in an in vitro adhesion
assay with mesothelial cells as most of the HA, and presumably the bound tumour cells, were lost from the mesothelial cells
during the washing steps of the assay. In order to try and clarify the situation, the adhesion of six ovarian tumour lines
to immobilized HA was measured. Four lines expressed high levels of CD44 and two lines expressed negligible amounts. Preliminary
experiments were carried out with one of the CD44-expressing lines. After coating a plate overnight with 3 mg ml-1 HA, the
5 min adhesion of this line varied between 2% and 73% according to the type of plate that was used. Falcon Micro Test III
flexible plates gave the highest adhesion and was used for further experiments. Plates were coated with concentrations of
HA between 0.001 mg ml−1 and 3 mg ml−1. All CD44 expressing lines adhered to HA, but the maximum adhesion and the adhesion
strength varied with the line studied and was not closely related to the total CD44 expression. These results suggest that
CD44 on ovarian tumour cells binds to HA on mesothelial cells. As much of the HA can be very easily lost from the mesothelial
cell surface, additional factors such as the strength of the CD44/HA interaction, and the formation of bonds by the tumour
cells with other membrane adhesion molecules, such as integrins, are also important in promoting tumour spread.
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献
944.
Carmel Daly Seamus Coyle Shirley McBride Lorraine O'Driscoll Noel Daly Kevin Scanlon Martin Clynes 《Cytotechnology》1996,19(3):199-205
Anmdr1 hammerhead was introduced into two adriamycin-selected multi-drug resistant human lung cell lines both of which over-express p-glycoprotein. Expression of the ribozyme resulted in a decrease inmdr1 mRNA expression and an increase in drug sensitivity in both cell lines. This would suggest that the use of specific ribozymes may represent an effective and specific approach in order to restore cellular sensitivity towards anti-cancer drugs. 相似文献
945.
目的探讨小细胞肺癌患者发生脑转移的相关因素。方法回顾性分析118例病理确诊的小细胞肺癌患者,比较发生脑转移与未发生脑转移两组小细胞肺癌患者的临床特征。结果单因素分析发现诊断时转移器官数、NSE、LDH、一线化疗周期数、一线化疗疗效、是否接受预防性全脑放疗与患者是否发生肺癌脑转移相关。多因素分析结果显示转移器官数、NSE、一线化疗周期数与接受预防性全脑放疗是脑转移的独立影响因素。结论转移器官数≥2[OR:4.53,(95%CI:1.19~17.26),P=0.027]和NSE大于正常值4倍[OR:2.70,(95%CI:1.05~6.94),P=0.039]是小细胞肺癌患者发生脑转移的独立危险因素。一线化疗周期数≥6个周期[OR:0.28,(95%CI:0.11~0.68),P=0.005]与接受预防性全脑放疗[OR:0.49,(95%CI:0.01~0.42),P=0.006]是脑转移的保护因素。 相似文献
946.
Lung cancer is a clinically difficult disease with rising disease burden around the world. Unfortunately, most lung cancers present at a clinically advanced stage. Of these cancers, many also present with brain metastasis which complicates the clinical picture. This review summarizes current knowledge on the molecular basis of lung cancer brain metastases. We start from the clinical perspective, aiming to provide a clinical context for a significant problem that requires much deeper scientific investigation. We review new research governing the metastatic process, including tumor cell signaling, establishment of a receptive tumor niches in the brain and evaluate potential new therapeutic options that take advantage of these new scientific advances.Lung cancer remains the largest single cause of cancer mortality in the United States (Siegel et al., 2015). This continues to be the clinical picture despite significant advances in therapy, including the advent of targeted molecular therapies and newly adopted immunotherapies for certain subtypes of lung cancer. In the vast majority of cases, lung cancer presents as advanced disease; in many instances, this advanced disease state is intimately associated with micro and macrometastatic disease (Goldberg et al., 2015). For both non-small cell lung cancer and small cell lung cancer patients, the predominant metastatic site is the brain, with up to 68% of patients with mediastinal lymph node metastasis eventually demonstrating brain metastasis (Wang et al., 2009).The frequency (incidence) of brain metastasis is highest in lung cancers, relative to other common epithelial malignancies (Schouten et al., 2002). Other studies have attempted to predict the risk of brain metastasis in the setting of previously non-metastatic disease. One of the largest studies to do this, analyzing historical data from 1973 to 2011 using the SEER database revealed a 9% risk of patients with previously non-metastatic NSCLC developing brain metastasis over the course of their disease, while 18% of small cell lung cancer patients without previous metastasis went on to develop brain metastasis as their disease progressed (Goncalves et al., 2016).The reasons underlying this predilection for the central nervous system, as well as the recent increase in the frequency of brain metastasis identified in patients remain important questions for both clinicians and basic scientists. More than ever, the question of how brain metastasis develop and how they can be treated and managed requires the involvement of interdisciplinary teams—and more importantly—scientists who are capable of thinking like clinicians and clinicians who are capable of thinking like scientists. This review aims to present a translational perspective on brain metastasis. We will investigate the scope of the problem of brain metastasis and the current management of the metastatic disease process in lung cancer. From this clinical starting point, we will investigate the literature surrounding the molecular underpinnings of lung tumor metastasis and seek to understand the process from a biological perspective to generate new hypotheses. 相似文献
947.
Ming-Hui Fan Qiang Zhu Hui-Hua Li Hyun-Jeong Ra Sonali Majumdar Dexter L. Gulick Jacob A. Jerome Daniel H. Madsen Melpo Christofidou-Solomidou David W. Speicher William W. Bachovchin Carol Feghali-Bostwick Ellen Puré 《The Journal of biological chemistry》2016,291(15):8070-8089
Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2–4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent with in vitro studies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP''s protective effects in the lung. 相似文献
948.
949.
950.
In medium containing low concentrations of serum, rat 13762NF mammary adenocarcinoma cell lines and clones (MTPa and MTC; isolated from the locally growing tumor) of low metastatic potential to lung did not exhibit a growth response to lung-conditioned medium, whereas a highly metastatic cell clone isolated from a spontaneous lung metastasis (MTLn3) did. The major growth-promoting factor for MTLn3 cells from porcine and rat lung-conditioned media was isolated by using a five-step procedure (anion exchange chromatography, Affi-gel blue affinity chromatography, chromatofocusing, size exclusion chromatography, and preparative native gel electrophoresis). The lung-derived factor that stimulated the growth of highly metastatic MTLn3 cells was a glycoprotein of Mr approximately 66,000 (non-reduced) or Mr approximately 72,000 (reduced) and possessed a pI of 6.9-7.0. It preferentially promoted the growth of lung-metastasizing tumor lines over their poorly lung-metastasizing counterparts in three tumor systems: rat 13762NF mammary adenocarcinoma, murine B16 melanoma, and murine RAW117 large-cell lymphoma. The factor's growth-stimulatory affect was inactivated by reduction or exposure to high temperature (95 degrees C). Although the growth factor appears to be glycosylated, its molecular weight was not altered by treatment with the protein-deglycosylating agent, trifluoromethane sulfonic acid. Cleavage of the protein by cyanogen bromide resulted in the formation of five fragments. Malignant cell response to this lung-derived paracrine growth factor may be important in the successful formation of lung metastases. 相似文献