PubMed · 3003989
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
D Bockus, F Remington, S Friedman, S Hammar. 1985. Electron microscopy what izzits.. https://doi.org/10.3109/01913128509055482
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
BACKGROUND: F-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) scanning has become a critically important tool in diagnosis and management of non-small-cell lung cancer. However, the effectiveness of (18)F-FDG-PET as a diagnostic tool for small-sized lung cancer is controversial. The purpose of this study was to examine the accuracy of( 18)F-FDG-PET in relation to Noguchi's classification in the diagnosis of small peripheral non-small-cell lung cancer. METHODS: Between January 2003 and April 2006, 150 patients with peripheral lung lesions who were undergoing chest computed tomography (CT),( 18)F-FDG-PET, and operation were analyzed. RESULTS: Eighty-three patients had malignant lesions, and 67 patients had benign lesions. PET had a sensitivity, specificity, positive predictive value, and negative predictive value of 75.9%, 64.1%, 72.4%, and 68.3%, respectively. In 37 patients with peripheral lung cancer measuring 2.0 cm or less in the greatest diameter, the sensitivity was 51.4% and the specificity was 51.9%. Among them, all 4 cases of Noguchi type A adenocarcinoma [localized bronchioloalveolar carcinoma (LBAC)], 4 of 5 type B and 8 of 17 type C were false negative, while 9 of 11 (81.8%) types D, E, and F (invasive carcinomas without a BAC component) were true positive. CONCLUSION: The accuracy of( 18)F-FDG-PET is generally low in distinguishing malignancy from benign lesions in small lesions (<2.0-cm diameter). The significance of PET as a diagnostic tool is small, especially when the tumor has a ground-glass component at a high rate. The sensitivity of PET is high in small invasive carcinomas without a BAC component, but it is difficult to distinguish carcinoma from benign tumor from its image.
Polycyclic aromatic hydrocarbons (PAHs) are potent carcinogens that require metabolic activation inside cells. The proximate carcinogens PAH-diols can be converted to o-quinones by aldo-keto reductases (AKRs) or to diol-epoxides by cytochrome P450 (P450) enzymes. We assessed the effect of benzo[a]pyrene-7,8-dihydrodiol (BPD) on proliferation in p53-null bronchoalveolar carcinoma H358 cells. BPD treatment led to a significant inhibition of proliferation and arrest in G2/M in H358 cells. The relative contribution of the AKR and P450 pathways to cell cycle arrest was assessed. Overexpression of AKR1A1 did not affect cell proliferation or cell cycle progression, and benzo[a]pyrene-7,8-dione did not cause any noticeable effect on cell growth, suggesting that AKR1A1 metabolic products were not involved in the antiproliferative effect of BPD. On the other hand, blockade of P450 induction or inhibition of P450 activity greatly impaired the effect of BPD. Moreover, P450 induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin significantly enhanced the antiproliferative effect of BPD. Mechanistic studies revealed that BPD caused a DNA damage response, Chk1 activation, and accumulation of phospho-Cdc2 (Tyr15) in H358 cells, effects that were impaired by an ataxia-telangectasia mutated (ATM)/ATM-related (ATR) inhibitor. Similar results were observed in human bronchoepithelial BEAS-2B cells, arguing for analogous mechanisms in tumorigenic and immortalized nontumorigenic cells lacking functional p53. Our data suggest that a p53-independent pathway operates in lung epithelial cells in response to BPD that involves P450 induction and subsequent activation of the ATR/ATM/Chk1 damage check-point pathway and cell cycle arrest in G2/M.
A single intratumoral injection of IL-12 and GM-CSF-loaded slow-release microspheres induces T cell-dependent eradication of established primary and metastatic tumors in a murine lung tumor model. To determine how the delivery of cytokines directly to the microenvironment of a tumor nodule induces local and systemic antitumor T cell activity, we characterized therapy-induced phenotypic and functional changes in tumor-infiltrating T cell populations. Analysis of pretherapy tumors demonstrated that advanced primary tumors were infiltrated by CD4+ and CD8+ T cells with an effector/memory phenotype and CD4+CD25+Foxp3+ T suppressor cells. Tumor-associated effector memory CD8+ T cells displayed impaired cytotoxic function, whereas CD4+CD25+Foxp3+ cells effectively inhibited T cell proliferation demonstrating functional integrity. IL-12/GM-CSF treatment promoted a rapid up-regulation of CD43 and CD69 on CD8+ effector/memory T cells, augmented their ability to produce IFN-gamma, and restored granzyme B expression. Importantly, treatment also induced a concomitant and progressive loss of T suppressors from the tumor. Further analysis established that activation of pre-existing effector memory T cells was short-lived and that both the effector/memory and the suppressor T cells became apoptotic within 4 days of treatment. Apoptotic death of pre-existing effector/memory and suppressor T cells was followed by infiltration of the tumor with activated, nonapoptotic CD8+ effector T lymphocytes on day 7 posttherapy. Both CD8+ T cell activation and T suppressor cell purge were mediated primarily by IL-12 and required IFN-gamma. This study provides important insight into how local IL-12 therapy alters the immunosuppressive tumor milieu to one that is immunologically active, ultimately resulting in tumor regression.