Nejvíce citovaný článek - PubMed ID 34806204
Using virtual microscopy for the development of sampling strategies in quantitative histology and design-based stereology
BACKGROUND: Scleral fixation of intraocular lenses is a surgical technique that involves anchoring an artificial lens to the sclera. Traditional approaches, such as capsular bag placement, may not be feasible in certain situations, making scleral fixation a valuable alternative. The scleral reactions to different types of suture materials are not fully understood. Therefore, the present study describes the microscopic structure of normal scleral tissue and its changes with suture materials. METHODS: We compared six groups of rabbit eyes focusing on the sclera: group with polytetrafluoroethylene (PTFE) chain, PTFE fiber, polypropylene (PPE) fiber and control groups. multilevel sampling and stereological methods were used for histological quantification of the leukocyte infiltration fractions and type I and type III collagen. RESULTS: Quantitative histological evaluation revealed the following: (1) For all materials used, inflammation was present in the surrounding scleral tissue compared with healthy controls. However, leukocyte infiltration in the sclera was not statistically different between the materials. (2) As part of the evaluation of collagen, the greatest changes occurred in the PTFE fiber group at 2 weeks postoperatively. In the PTFE chain group, more significant changes were visible at 4 weeks. (3) The changes in the PPE fiber group compared to healthy scleral tissue were the least significant. CONCLUSIONS: From a histological point of view, it is evident that there are differences in the quantitative parameters between the untouched sclera and the sclera with suture material. Furthermore, distinctions were observed among various materials and across different time intervals.
- Klíčová slova
- histology, rabbit, sclera, scleral fixation of intraocular lens, stereology,
- MeSH
- králíci MeSH
- modely u zvířat MeSH
- polypropyleny škodlivé účinky MeSH
- polytetrafluoroethylen škodlivé účinky MeSH
- skléra * patologie MeSH
- sutura * škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- polypropyleny MeSH
- polytetrafluoroethylen MeSH
BACKGROUND: A current topic of ma jor interest in regenerative medicine is the development of novel materials for accelerated healing of sutures, and nanofibers seem to be suitable materials for this purpose. As various studies have shown, nanofibers are able to partially substitute missing extracellular matrix and to stimulate cell proliferation and differentiation in sutures. Therefore, we tested nanofibrous membranes and cryogenically fractionalized nanofibers as potential materials for support of the healing of intestinal anastomoses in a rabbit model. MATERIALS AND METHODS: We compared cryogenically fractionalized chitosan and PVA nanofibers with chitosan and PVA nanofiber membranes designed for intestine anastomosis healing in a rabbit animal model. The anastomoses were biomechanically and histologically tested. RESULTS: In strong contrast to nanofibrous membranes, the fractionalized nanofibers did show positive effects on the healing of intestinal anastomoses in rabbits. The fractionalized nanofibers were able to reach deep layers that are key to increased mechanical strength of the intestine. Moreover, fractionalized nanofibers led to the formation of collagen-rich 3D tissue significantly exceeding the healing effects of the 2D flat nanofiber membranes. In addition, the fractionalized chitosan nanofibers eliminated peritonitis, significantly stimulated anastomosis healing and led to a higher density of microvessels, in addition to a larger fraction of myofibroblasts and collagen type I and III. Biomechanical tests supported these histological findings. CONCLUSION: We concluded that the fractionalized chitosan nanofibers led to accelerated healing for rabbit colorectal anastomoses by the targeted stimulation of collagen-producing cells in the intestine, the smooth muscle cells and the fibroblasts. We believe that the collagen-producing cells were stimulated both directly due to the presence of a biocompatible scaffold providing cell adhesion, and indirectly, by a proper stimulation of immunocytes in the suture.
- Klíčová slova
- collagen, colorectal anastomoses, cryogenic grinding, electrospinning, microvessels,
- MeSH
- chitosan * farmakologie MeSH
- hojení ran MeSH
- kolagen farmakologie MeSH
- králíci MeSH
- nanovlákna * MeSH
- tlusté střevo MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chitosan * MeSH
- kolagen MeSH
Non-Hodgkin lymphomas (NHL) represent the most common hematologic malignancies. Patient-derived xenografts (PDXs) are used for various aspects of translational research including preclinical in vivo validation of experimental treatment approaches. While it was repeatedly demonstrated that PDXs keep majority of somatic mutations with the primary lymphoma samples, from which they were derived, the composition of PDX tumor microenvironment (TME) has not been extensively studied. We carried out a comparative genetic and histopathological study of 15 PDX models derived from patients with various types of NHL including diffuse large B-cell lymphoma (DLBCL; n = 7), Burkitt lymphoma (BL; n = 1), mantle cell lymphoma (MCL; n = 2), and peripheral T-cell lymphomas (PTCL; n = 5). Whole exome sequencing (WES) of the PDXs and primary lymphoma cells was implemented in 13 out of 15 cases with available DNA samples. Standard immunohistochemistry (IHC) was used to analyze the composition of PDX TME. WES data confirmed that PDXs maintained the genetic heterogeneity with the original primary lymphoma cells. In contrast, IHC analysis revealed the following recurrently observed alterations in the composition of PDX tumors: more blastoid lymphoma cell morphology, increased proliferation rate, lack of non-malignant cellular components including T cells and (human or murine) macrophages, and significantly lower intratumoral microvessel density and microvessel area composed of murine vessels. In addition, PDX tumors derived from T-NHL displayed additional differences compared to the primary lymphoma samples including markedly lower desmoplasia (i.e., the extent of both reticular and collagen fibrosis), loss of expression of cytotoxic granules (i.e., perforin, TIA, granzyme B), or loss of expression of T-cell specific antigens (i.e., CD3, CD4, CD8). Our data suggest that despite keeping the same genetic profiles, PDX models of aggressive NHL do not recapitulate the microenvironmental heterogeneity of the original lymphomas. These findings have implications on the relevance of PDX models in the context of preclinical research.
- MeSH
- difúzní velkobuněčný B-lymfom * MeSH
- dospělí MeSH
- heterografty MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nádorové mikroprostředí MeSH
- protinádorové látky * MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- protinádorové látky * MeSH
In this retrospective study on 67 patients with hepatocellular carcinoma (HCC), after tumor resection, we evaluated the significance of CD3+ and CD8+ T-lymphocytes and CD20+ B-lymphocytes in tumor and non-tumor liver for time to recurrence (TTR), disease-free survival (DFS) and overall survival. After immunohistochemical staining, the density of nucleated lymphocyte profiles (QA) was estimated stereologically in the tumor center (TC), inner margin (inn M), outer margin (out M), peritumor and non-tumor liver. In TC, intermediate and high QA of CD8+ cells predicted longer TTR, whereas CD3+ and CD20+ were predictive only at high QA. DFS was predicted by high QA of CD3+, CD8+ and CD20+ cells in TC. The inn M harbored smaller QA of CD3+, CD8+ and CD20+ lymphocytes than out M. In contrast to out M, high T-cells' QA and intermediate and high B-cell QA in inn M predicted longer TTR and DFS. High inn M/out M QA ratios of CD3+ and CD20+ cells were associated with longer TTR and DFS, whereas high inn M/out M QA ratio of CD8+ was predictive only for DFS. Patients with intermediate-high QA of combined CD8+ and CD20+ cells in inn M showed longer TTR and DFS, compared to CD8+-high or CD20+-high alone. Our findings highlight overall heterogeneity of the tumor invasive margin, the importance of inn M, and the predictive role of B-cells.
- Klíčová slova
- B-cells, T-cells, disease-free survival, hepatocellular carcinoma, heterogeneity, prognosis, stereology, time to recurrence, tumor invasive margin, tumor-infiltrating lymphocytes,
- Publikační typ
- časopisecké články MeSH