scholarly journals Preclinical Model of Stereotactic Ablative Lung Irradiation Using Arc Delivery in the Mouse: Is Fractionation Worthwhile?

2021 ◽  
Vol 8 ◽  
Author(s):  
Annaïg Bertho ◽  
Morgane Dos Santos ◽  
Sarah Braga-Cohen ◽  
Valérie Buard ◽  
Vincent Paget ◽  
...  
Keyword(s):  
Lung Fibrosis ◽  
Laboratory Data ◽  
Preclinical Model ◽  
High Dose ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Fractionation Schedule ◽  
Arc Therapy ◽  
Lung Irradiation ◽  
Beam Collimation

Lung stereotactic body radiation therapy is characterized by a reduction in target volumes and the use of severely hypofractionated schedules. Preclinical modeling became possible thanks to rodent-dedicated irradiation devices allowing accurate beam collimation and focal lung exposure. Given that a great majority of publications use single dose exposures, the question we asked in this study was as follows: in incremented preclinical models, is it worth using fractionated protocols or should we continue focusing solely on volume limitation? The left lungs of C57BL/6JRj mice were exposed to ionizing radiation using arc therapy and 3 × 3 mm beam collimation. Three-fraction schedules delivered over a period of 1 week were used with 20, 28, 40, and 50 Gy doses per fraction. Lung tissue opacification, global histological damage and the numbers of type II pneumocytes and club cells were assessed 6 months post-exposure, together with the gene expression of several lung cells and inflammation markers. Only the administration of 3 × 40 Gy or 3 × 50 Gy generated focal lung fibrosis after 6 months, with tissue opacification visible by cone beam computed tomography, tissue scarring and consolidation, decreased club cell numbers and a reactive increase in the number of type II pneumocytes. A fractionation schedule using an arc-therapy-delivered three fractions/1 week regimen with 3 × 3 mm beam requires 40 Gy per fraction for lung fibrosis to develop within 6 months, a reasonable time lapse given the mouse lifespan. A comparison with previously published laboratory data suggests that, in this focal lung irradiation configuration, administering a Biological Effective Dose ≥ 1000 Gy should be recommended to obtain lung fibrosis within 6 months. The need for such a high dose per fraction challenges the appropriateness of using preclinical highly focused fractionation schedules in mice.

The Identification of Phospholipid Micelles in Glutaraldehyde-Urea Embedded Tissue

1975 ◽  
Vol 33 ◽  
pp. 494-495
Author(s):  
Daniel C. Pease
Keyword(s):  
Electron Micrographs ◽  
Lung Tissue ◽  
Osmium Tetroxide ◽  
Uranyl Acetate ◽  
Type Ii ◽  
Lead Citrate ◽  
Phospholipid Micelles ◽  
Type Ii Pneumocytes ◽  
Ultrathin Sections ◽  
Polar Water

It is reasonable to think that phospholipid micelles should be visible and identifiable in electron micrographs of ultrathin sections if only they can be preserved throughout the embedding process. The development of highly polar, water-containing, aminoplastic embedments has made this a likely possibility. With this in mind, an investigation of the lecithin-secreting, Type II pneumocytes of the lung is underway.Initially it has been easiest to recognize phospholipid micelles in lung tissue fixed first with glutaraldehyde, and then secondarily exposed to osmium tetroxide. However, the latter is not a necessary concomitant for micellar preservation. Conventional uranyl acetate and lead citrate staining is finally applied. Importantly, though, the micelles have been most easily seen in tissue embedded in 507. glutaraldehyde polymerized with urea, as described in detail by D.C. Pease and R.G. Peterson (J. Ultra- struct. Res., 41, 133, 1972). When oriented appropriately, the micellar units are seen as tiny, bilayer plates.

Flow cytometric identification and isolation of hypertrophic type II pneumocytes after partial pneumonectomy

1989 ◽  
Vol 257 (3) ◽  
pp. C528-C536 ◽  
Author(s):  
B. D. Uhal ◽  
S. R. Rannels ◽  
D. E. Rannels
Keyword(s):  
Gradient Centrifugation ◽  
Type Ii Cells ◽  
Type Ii ◽  
Acridine Orange Staining ◽  
Flow Cytometric ◽  
Percoll Density Gradient Centrifugation ◽  
Type Ii Pneumocytes ◽  
The Mean ◽  
Cellular Dna ◽  
The Right

Type II pneumocytes were isolated by either Percoll density gradient centrifugation or by immunoglobulin G (IgG) panning from the lungs of normal rats and the right lung of rats subjected to left pneumonectomy. Cells were studied at 7- (pnx-7) and 15- (pnx-15) days postoperative, times during and after, respectively, rapid compensatory growth of the right lung. Acridine orange staining permitted resolution of type II cells from contaminants on the basis of high red fluorescence (greater than 590 nm). Simultaneous measurement of forward-angle light scatter (FALS) suggested a shift of pnx-7 cells toward greater size, which was reversed in pnx-15 cells. By Percoll gradient isolation, approximately 15% of pnx-7 cells analyzed were above the mean FALS of control cells. In contrast, approximately 30% of the pnx-7 cells isolated by IgG panning were above the mean FALS of corresponding control cells. Biochemical analyses of pnx-7 cells separated by cell sorting into "high FALS" and "low FALS" subgroups revealed that high FALS type II cells contained 50% more protein (P less than 0.05) and 140% more RNA (P less than 0.01) than low FALS cells, with no significant change in cellular DNA content. These data are consistent with previous studies of type II cells isolated from the lungs of pneumonectomized animals and confirm the presence of hypertrophic cells in these preparations. They provide a foundation from which to design further flow cytometric studies of the role of hypertrophic type II pneumocytes in compensatory lung growth.

scholarly journals [18F]FMISO PET/CT imaging of hypoxia as a non-invasive biomarker of disease progression and therapy efficacy in a preclinical model of pulmonary fibrosis: comparison with the [18F]FDG PET/CT approach

2021 ◽  
Author(s):  
Julie Tanguy ◽  
Françoise Goirand ◽  
Alexanne Bouchard ◽  
Jame Frenay ◽  
Mathieu Moreau ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Disease Progression ◽  
Lung Fibrosis ◽  
Ct Imaging ◽  
Significant Feature ◽  
Preclinical Model ◽  
Lung Density ◽  
Intratracheal Administration ◽  
Therapy Efficacy ◽  
Pet Ct

Abstract Purpose Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor outcome and limited therapeutic options. Imaging of IPF is limited to high-resolution computed tomography (HRCT) which is often not sufficient for a definite diagnosis and has a limited impact on therapeutic decision and patient management. Hypoxia of the lung is a significant feature of IPF but its role on disease progression remains elusive. Thus, the aim of our study was to evaluate hypoxia imaging with [18F]FMISO as a predictive biomarker of disease progression and therapy efficacy in preclinical models of lung fibrosis in comparison with [18F]FDG. Methods Eight-week-old C57/BL6 mice received an intratracheal administration of bleomycin (BLM) at day (D) 0 to initiate lung fibrosis. Mice received pirfenidone (300 mg/kg) or nintedanib (60 mg/kg) by daily gavage from D9 to D23. Mice underwent successive PET/CT imaging at several stages of the disease (baseline, D8/D9, D15/D16, D22/D23) with [18F]FDG and [18F]FMISO. Histological determination of the lung expression of HIF-1α and GLUT-1 was performed at D23. Results We demonstrate that mean lung density on CT as well as [18F]FDG and [18F]FMISO uptakes are upregulated in established lung fibrosis (1.4-, 2.6- and 3.2-fold increase respectively). At early stages, lung areas with [18F]FMISO uptake are still appearing normal on CT scans and correspond to areas which will deteriorate towards fibrotic lesions at later timepoints. Nintedanib and pirfenidone dramatically and rapidly decreased mean lung density on CT as well as [18F]FDG and [18F]FMISO lung uptakes (pirfenidone: 1.2-, 2.9- and 2.6-fold decrease; nintedanib: 1.2-, 2.3- and 2.5-fold decrease respectively). Early [18F]FMISO lung uptake was correlated with aggressive disease progression and better nintedanib efficacy. Conclusion [18F]FMISO PET imaging is a promising tool to early detect and monitor lung fibrosis progression and therapy efficacy.

scholarly journals Pulmonary surfactant secretion in type II pneumocytes in the existence of inflammatory cells

1990 ◽  
Vol 52 ◽  
pp. 184
Author(s):  
Yoshiaki Oda ◽  
Hirofumi Kai ◽  
Kazunori Takaki ◽  
Tae Yasunaga ◽  
Kouichirou Murahara ◽  
...  
Keyword(s):  
Pulmonary Surfactant ◽  
Inflammatory Cells ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Surfactant Secretion

scholarly journals Dosimetric Comparison between High Dose Rate Brachytherapy Boost and Volumetric Arc Therapy Boost in Locally Advanced Cancer Cervix

2021 ◽  
Vol 07 (02) ◽  
pp. 085-088
Author(s):  
Hanady Hegazy ◽  
Neamat Hegazy ◽  
Maher Soliman ◽  
Amr Elsaid
Keyword(s):  
Small Bowel ◽  
Dose Rate ◽  
Advanced Cancer ◽  
Locally Advanced ◽  
Target Volume ◽  
High Dose Rate ◽  
High Dose ◽  
Cancer Cervix ◽  
Arc Therapy ◽  
Locally Advanced Cancer

AbstractConcurrent chemoradiotherapy is considered the standard treatment for the locally advanced cancer cervix (LACC). Radiotherapy is commonly administered by a three-dimensional conformal radiotherapy (3DCRT) approach followed by brachytherapy (BT). High dose rate (HDR) BT is commonly administered; however, several drawbacks exist including invasive technique, pain, requirement of anesthesia, and operative risks. We assessed the dosimetric difference between the HDR BT and the volumetric modulated arc therapy (VMAT) boost in those patients. Ten patients were selected retrospectively with LACC and all received whole pelvis radiotherapy followed by BT boost of 7 Gy in three fractions. The computed tomography (CT) image was transferred to the Varian system for the VMAT plan while the one with the applicator was transferred to the Sagi planning system and the high-risk clinical target volume (HR-CTV), bladder, rectum, sigmoid, and small bowel were delineate with a margin of 5 mm were added to the CTV to create the planning target volume (PTV). The D90 for the PTV in VMAT boost was lower than received by the HR-CTV in the BT boost. Mean volume of the PTV was higher than that of the HR-CTV. The D2cc was higher in VMAT for bladder, sigmoid, and rectum while the D2cc for the small bowel in BT was higher compared with the VMAT. The VMAT is an option that exists for patients who refuse BT or cannot tolerate it, or in case of nonavailability of BT or a nonworking machine.

scholarly journals Plutonium-induced Proliferative Lesions and Pulmonary Epithelial Neoplasms in the Rat: Immunohistochemical and Ultrastructural Evidence for Their Origin from Type II Pneumocytes

1994 ◽  
Vol 31 (3) ◽  
pp. 366-374 ◽  
Author(s):  
R. A. Herbert ◽  
B. S. Stegelmeier ◽  
N. A. Gillett ◽  
A. H. Rebar ◽  
W. W. Carlton ◽  
...  
Keyword(s):  
Clara Cell ◽  
Normal Lung ◽  
Type Ii ◽  
Epithelial Hyperplasia ◽  
Cell Antigen ◽  
Alveolar Epithelial ◽  
Type Ii Pneumocytes ◽  
Epithelial Neoplasms ◽  
Epithelial Lesions ◽  
Surfactant Apoprotein

Immunohistochemistry and transmission electron microscopy were used to clarify the cellular origin for plutonium-239-induced pulmonary proliferative (preneoplastic) epithelial lesions and epithelial neoplasms in F344 rats. Examples of each histologic type of proliferative lesion and neoplasm were stained by the avidin-biotin complex immunoperoxidase method using antibodies to rat surfactant apoprotein and Clara cell antigen. Rat surfactant apoprotein immunostaining was detected in type II pneumocytes in sections of normal lung, in the cells of the proliferative lesions classified histologically as alveolar epithelial hyperplasia (51) and mixed foci (alveolar epithelial hyperplasia with fibrosis) (30), and in adenomas (2), adenocarcinomas (3), and adenosquamous carcinomas (2). With the exception of one adenosquamous carcinoma, Clara cell antigen immunostaining was not detected in any of the pulmonary lesions but was detected in nonciliated cuboidal epithelial (Clara) cells in normal bronchioles. The epithelial cells of the proliferative lesions and neoplasms had ultrastructural features consistent with type II pneumocytes, i.e., the presence of cytoplasmic lamellar and multivesicular bodies. The results of these studies indicate that the majority of plutonium-induced proliferative epithelial lesions and neoplasms in the rat originate from alveolar type II pneumocytes.

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