Journal articles on the topic 'Immunohisto-chemistry'
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Takenoue, T., J. Kitayama, Y. Takei, N. Umetani, K. Matsuda, M. E. Nita, K. Hatano, T. Tsuruo, and H. Nagawa. "Characterization of dihydropyrimidine dehydrogenase on immunohisto-chemistry in colon carcinoma, and correlation between immunohisto-chemical score and protein level or messenger RNA expression." Annals of Oncology 11, no. 3 (March 2000): 273–80. http://dx.doi.org/10.1023/a:1008337913456.
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WATTLE, O. "Cytokeratins of the equine hoof wall, chestnut and skin: bio- and immunohisto-chemistry." Equine Veterinary Journal 30, S26 (June 10, 2010): 66–80. http://dx.doi.org/10.1111/j.2042-3306.1998.tb05124.x.
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A.MADEJ, JANUSZ. "Usefulness of immunohisto(cyto)chemistry, antigens and cell marker detection in cancer diagnosis and histogenesis." Medycyna Weterynaryjna 74, no. 09 (2018): 6129–2018. http://dx.doi.org/10.21521/mw.6129.
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It was shown that the unification of neoplastic nomenclature could be very challenging. It was also noted that neoplastic disease is a dual disease, involving both the presence of neoplastic cells in the organism and the resulting disturbances in the functioning of the immune system. The study also follows the principle that the general markers are examined before the specific ones, especially in neoplasms of unknown origin or those suspected of endocrine secretion, such as carcinoid tumours.
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Pusiol, Teresa, Maria Grazia Zorzi, Doriana Morichetti, and Francesco Piscioli. "Routine Use of Immunohisto-chemistry May Increase the Frequency of Hybrid Peripheral Nerve Sheath Tumors." American Journal of Dermatopathology 33, no. 6 (August 2011): 634–36. http://dx.doi.org/10.1097/dad.0b013e318200f722.
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Gnaegi, H. "Cryo Ultramicrotomy of Biological Samples and Polymers." Microscopy and Microanalysis 6, S2 (August 2000): 314–15. http://dx.doi.org/10.1017/s1431927600034061.
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IntroductionCryo Ultramicrotomy gains increasing importance for immunocyto- and immunohisto- chemistry, element analysis, morphological studies and other investigations.Major advances in immunocyto-chemistry and the sectioning of frozen hydrated specimens have been realized with the appropriate instrumentation and tools (1,2).In immuno-electron microscopy it has been found that a considerable reduction of structural damage in tissue and cells can be obtained with a modified sectioning and pick-up method using sucrose/methyl cellulose solution (3, 4).In recent years various scientists have tried to understand cryo sectioning and the problems related to the cry-osectioning process (5, 6, 7, 8).A promising attempt to eliminate one of the major artefacts in ultramicrotomy, that of compression", was made with the development of the oscillating diamond knife (9).In polymer research cryo ultramicrotomy is a well established technique.However, only little information is available about the the cryo sectioning process for the following reasons: Much cryo sectioning is performed in polymer companies.
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Shvorob, D. S., T. I. Shevchenko, and R. B. Kondratyk. "Diagnosis of molecular subtypes of colorectal cancer using immunohistochemistry." CLINICAL AND EXPERIMENTAL MORPHOLOGY 10, no. 3 (2021): 14–20. http://dx.doi.org/10.31088/cem2021.10.3.14-20.
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Colorectal cancer ranks third in the morbidity structure among all malignant tumors and includes sporadic and hereditary neoplasms. Cancer genome sequencing has revealed numerous mutation variants that determine the ways colorectal carcinoma progresses. The course, prognosis, and management strategy of the disease vary greatly depending on the subtype of a molecular tumor. This literature review discusses the latest data on the variants of colorectal cancer oncogenesis and presents the phenotypic model classification based on them. Immunohistochemistry (IHC) is suggested for determining the individual tumor characteristics. The article also clarifies the Bethesda panel used to detect microsatellite instability, markers for Lynch syndrome, and a list of IHC markers for determining the phenotypic model of colorectal carcinoma. Keywords: colorectal cancer, phenotypic models, consensus molecular subtypes (CMS), immunohisto-chemistry, Bethesda panel, Lynch syndrome
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Shvorob, D. S., T. I. Shevchenko, and R. B. Kondratyk. "Diagnosis of molecular subtypes of colorectal cancer using immunohistochemistry." CLINICAL AND EXPERIMENTAL MORPHOLOGY 10, no. 3 (2021): 14–20. http://dx.doi.org/10.31088/cem2021.10.3.14-20.
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Colorectal cancer ranks third in the morbidity structure among all malignant tumors and includes sporadic and hereditary neoplasms. Cancer genome sequencing has revealed numerous mutation variants that determine the ways colorectal carcinoma progresses. The course, prognosis, and management strategy of the disease vary greatly depending on the subtype of a molecular tumor. This literature review discusses the latest data on the variants of colorectal cancer oncogenesis and presents the phenotypic model classification based on them. Immunohistochemistry (IHC) is suggested for determining the individual tumor characteristics. The article also clarifies the Bethesda panel used to detect microsatellite instability, markers for Lynch syndrome, and a list of IHC markers for determining the phenotypic model of colorectal carcinoma. Keywords: colorectal cancer, phenotypic models, consensus molecular subtypes (CMS), immunohisto-chemistry, Bethesda panel, Lynch syndrome
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Melendez, Mark M., Xiaoti Xu, Steve A. Mcclain, and Su-I. Daniel Huang. "Atypical fibroxanthoma in a young woman: An unusual case presentation." Canadian Journal of Plastic Surgery 15, no. 3 (September 2007): 169–72. http://dx.doi.org/10.1177/229255030701500302.
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Atypical fibroxanthoma (AFX) is an uncommon neoplasm, identified as a spindle cell tumour that is generally found in elderly patients on sun-exposed areas. The majority of cases of AFX are benign, and metastasis is a rare phenomenon. The first case in the literature of AFX is described in a young woman with no previous risk factors who presented with a three-month history of an enlarging nodule of the left nasal alar. Excision showed the lesion to be composed of hyperchromatic, pleomorphic, vacuolated spindle cells and multinucleated giant cells. The tumour cells stained positive for macrophage-histiocyte antigen alpha1-antitrypsin, neurokinin-1, CD68 and alpha1-antichymotrypsin. The present case report highlights the importance of correct diagnosis for AFX with adequate excision and by considering the histopathology and immunohisto-chemistry of its clinical differential diagnosis.
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Wilkins, Pamela A., Peggy S. Marsh, Helen Acland, and Fabio Del Piero. "Listeria Monocytogenes Septicemia in a Thoroughbred Foal." Journal of Veterinary Diagnostic Investigation 12, no. 2 (March 2000): 173–76. http://dx.doi.org/10.1177/104063870001200216.
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Listeria monocytogenes septicemia was diagnosed in a 6-day-old Thoroughbred foal. Primary clinical signs included fever, depression, diarrhea, and respiratory distress. Hematologic abnormalities included leukopenia, neutropenia, degenerative left shift, and hyperfibrinogenemia. Clinical chemistry and blood gas abnormalities included metabolic acidosis, hypoxemia, hypocapnia, hypoglycemia, and hyponatremia. Despite aggressive therapeutic intervention and intensive care, the foal died within 12 hours of admission. A postmortem examination was performed, and the primary gross lesion was bilaterally severe, focally extensive bronchopneumonia. Histopathology revealed severe subacute multifocal suppurative bronchopneumonia with necrotizing vasculitis and intralesional coccobacilli. Cultures of blood collected at admission and immediately prior to death were positive for L. monocytogenes, as were cultures obtained from lung and liver at necropsy. Immunohisto-chemical examination of formalin-fixed tissues revealed abundant intra- and extracellular L. monocytogenes antigen within the lung and intravascularly in multiple organs.
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Nicholson, Eric M., Robert A. Kunkle, Amir N. Hamir, Semakaleng Lebepe-Mazur, and Dennis Orcutt. "Detection of the Disease-Associated Isoform of the Prion Protein in Formalin-Fixed Tissues by Western Blot." Journal of Veterinary Diagnostic Investigation 19, no. 5 (September 2007): 548–52. http://dx.doi.org/10.1177/104063870701900515.
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Clinical signs of prion disease are not specific and include a variety of differential diagnoses. Serological tests and nucleic acid-based detection methods are not applicable to prion-disease-agent detection because of the unusual nature of the infectious agent. Prion-disease diagnosis is primarily conducted by means of immunodetection of the infectious agent, typically by at least 2 distinct procedures with immunohisto-chemistry and Western blot being the most informative. These approaches differ in the need for formalin-fixed and frozen or fresh tissue respectively. This work describes a method for the detection of the disease-associated isoform of the prion protein by Western blot using formalin-fixed tissues. The approach requires only minimal modification of existing Western-blot procedures and could readily be incorporated into existing detection schemes for confirmatory purposes when fresh or frozen tissues are unavailable.
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Kim, Jong Sik, and Geoffrey Daniel. "VARIATIONS IN CELL WALL ULTRASTRUCTURE AND CHEMISTRY IN CELL TYPES OF EARLYWOOD AND LATEWOOD IN ENGLISH OAK (QUERCUS ROBUR)." IAWA Journal 37, no. 3 (September 7, 2016): 383–401. http://dx.doi.org/10.1163/22941932-20160142.
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Although there is considerable information on anatomy and gross chemistry of oak wood, little is known on the ultrastructure and chemistry at the individual cell wall level. In particular, differences in ultrastructure and chemistry within the same cell type between earlywood (EW) and latewood (LW) are poorly understood. This study investigated the ultrastructure and chemistry of (vasicentric) tracheids, vessels, (libriform) fibers and axial/ray parenchyma cells of English oak xylem (Quercus robur L.) using light-, fluorescence- and transmission electron microscopy combined with histo/cytochemistry and immunohisto/ cytochemistry. EW tracheids showed several differences from LW tracheids including thinner cell walls, wider middle lamella cell corner (MLcc) regions and lesser amounts of mannan epitopes. Fibers showed thicker cell walls and higher amounts of mannan epitopes than tracheids. EW vessels were rich in guaiacyl (G) lignin with a characteristic non-layered cell wall organization (absence of S1–3 layers), whereas LW vessels were rich in syringyl (S) lignin with a three layered cell wall structure (S1–3 layers). Formation of a highly lignified and wide protective layer (PL) inside axial/ray parenchyma cells was detected only in EW. Distribution of mannan epitopes varied greatly between cell types and between EW and LW, whereas distribution of xylan epitopes was almost identical in all cell types within a growth ring. Together, this study demonstrates that there are great variations in ultrastructure and chemistry of cell walls within a single growth ring of English oak xylem.
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Yang, Long, and Xiu-Juan Dong. "Potential role of P2X7 receptor in regulating kidney stem cells in the course of acute kidney injury." Bangladesh Journal of Pharmacology 11, no. 4 (October 22, 2016): 869. http://dx.doi.org/10.3329/bjp.v11i4.24390.
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<p class="Abstract">The role of the P2X7R in developing acute kidney injury is unknown. In this study, we developed acute kidney injury mouse model system using 0.75% adenine and examined for renal damage using histology on day 2 and day 4. P2X7 antagonist (A438079) was used to study the recovery process after initial damage and it shows positive histological data. The P2X7R expression on the day 2 and day 4 of acute kidney injury was studied using immunohisto-chemistry and Western blotting. Result shows elevated expression as acute kidney injury progress. Later the P2X7R expression was compared with apoptotic signal and stem cell specific marker (CD133). The results conclude that the apoptotic signals are mainly associated with advanced stage of acute kidney injury but not much in day 2. Similarly, CD133 expression was mask-ed in latter stages of injury following elevated expression in the initial stages.</p><p> </p>
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Paudyal, P., TN Subba, A. Pradhan, S. Dhakal, S. Karki, and P. Paudyal. "Extraordinarily Large Malignant Extra Gastro Intestinal Stromal Tumor Presenting as an Abdominal Mass." Journal of BP Koirala Institute of Health Sciences 2, no. 2 (December 31, 2019): 84–87. http://dx.doi.org/10.3126/jbpkihs.v2i2.27875.
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Background: Gastrointestinal stromal tumors (GIST) are rare of all gastrointestinal neoplasms with histology and immunohistochemistry similar to gastrointestinal stromal tumors. They occur outside the gastrointestinal tract rarely and are, hence, called the extra gastrointestinal stromal tumors (EGIST). Herein, we report a rare case of malignant extra intestinal gastrointestinal tumor.
Case report: A 39 yr old female presented to the surgical OPD with a lump in the abdomen since 4 months. We received a lobulated tumor which measured 40x25x20 cm3 and showed capsule. Cut surface was predominantly solid, grey white with areas of hemorrhage and necrosis along with cystic areas. Histopathology and immunohisto chemistry revealed it to be a malignant EGIST of mesentery because of no continuity of the tumor with the small intestine microscopically.
Conclusion: EGIST is a rare no epithelial tumor of mesentery. Omentum histopathological examination is a standard technique to diagnose the tumor and to differentiate it immunohistochemically from other tumors having similar morphology. Correct diagnosis plays valuable role in the treatment.
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Epstein, E., J. Silver, G. Almogi, N. Livni, and T. Naveh-Many. "Parathyroid hormone mRNA levels are increased by progestins and vary during rat estrous cycle." American Journal of Physiology-Endocrinology and Metabolism 270, no. 1 (January 1, 1996): E158—E163. http://dx.doi.org/10.1152/ajpendo.1996.270.1.e158.
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Estrogen increases parathyroid hormone (PTH) mRNA levels in vivo in ovariectomized rats. We now show that the 19-norprogestin R-5020 given to weanling rats or mature ovariectomized rats led to a twofold increase in thyroparathyroid PTH mRNA levels. This increase in PTH mRNA occurred at 24 and 48 h after progesterone but not at 72 h. There were no changes in serum calcium. In vitro, in primary cultures of bovine parathyroid cells, progesterone increased PTH mRNA levels threefold at 10(-8) M and twofold at 10(-9) M after 24 h. Progesterone receptor (PR) mRNA was demonstrated in rat parathyroid tissue by in situ hybridization and in human parathyroid adenoma by immunohisto-chemistry. Changes in PTH mRNA levels during the rat estrous cycle were also studied. At proestrus and estrus PTH mRNA levels were increased significantly by three- and fourfold compared with diestrus. Our results confirm that the parathyroid gland is a target organ for the ovarian sex steroids estrogen and progesterone and are of physiological relevance as shown by the changes during estrus.
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Pusiol, Teresa, Doriana Morichetti, Maria Grazia Zorzi, and Francesco Piscioli. "Limited Value of Immunohisto-chemistry in Diagnostic Differentiation Between Clear Cell Atypical Fibroxanthoma and Distinctive Clear Cell Mesenchymal Neoplasm With Atypical Features." American Journal of Dermatopathology 34, no. 2 (April 2012): 227–28. http://dx.doi.org/10.1097/dad.0b013e31821ff4e8.
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Singh, Nitya. "NEUROENDOCRINE CARCINOMA AS SINONASAL MALIGNANCY." UP STATE JOURNAL OF OTOLARYNGOLOGY AND HEAD AND NECK SURGERY VOLUME 7, VOLUME 7 NUMBER 2 NOV 2018 (November 1, 2019): 30–34. http://dx.doi.org/10.36611/upjohns/19.7.
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Neuroendocrine neoplasms are defined as epithelial neoplasms with predominant neuroendocrine differentiation. Extremely rare site for neuroendocrine carcinoma are nasal cavity and paranasal sinuses and are aggressive neoplasm with a high recurrence rate and a tendency to metastasize. A 19-year male presented to the department of Otorhinolaryngology with left nasal obstruction, persistent headache for nine months and on and off bleeding from left nasal cavity for 2 months. On examination of the nasal cavity, a gross deviation of nasal septum with a red, friable, gelatinous, polypoidal mass with a tendency to bleed was seen in the left nasal cavity. The patient underwent endoscopic excision of mass under GA. Specimen was sent for histopathological examination which exhibited the properties of Neuro-endocrine carcinoma. Sinonasal NEC is an extremely rare malignancy. CT scan with intravenous contrast is the most effectual early imaging study, additionally MRI will further make a fine description of the tumor extension. Furthermore, Immunohisto-chemistry is an important tool that can be valuable in reaching a diagnosis. There is no clear recommendation regarding the treatment of the sinonasal neuroendocrine carcinoma, but the multimodal approach with proper counselling of patient is favoured and generally accepted.
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Wu, Gaoliang, Chao Hao, Xueliang Qi, and Jianqiang Nie. "Effect of Yes Associated Protein 1 Silence on Proliferation and Apoptosis of Bladder Cancer Cells." Journal of Biomaterials and Tissue Engineering 11, no. 5 (May 1, 2021): 857–63. http://dx.doi.org/10.1166/jbt.2021.2637.
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Yes Associated Protein 1 (YAP) can act as either an oncoprotein or a tumor suppressor in different cellular contexts. However, the reports about the direct role of YAP silence in bladder cancer cells are rare. We designed loss-off-function experiments to investigate the effect of YAP knockdown on bladder cancer cell proliferation, cell cycle and cell apoptosis. We examined YAP expression in human bladder cancer and paracancerous tissues using RT-qPCR, western blot and immunohisto-chemistry. YAP short hairpin RNA (shRNA) was successfully constructed and transfected into T24 cells to knockdown YAP. Cell proliferation, cell cycle and cell apoptosis were analyzed by CCK-8 and flow cytometry. We found the expression levels of YAP mRNA and protein were significantly increased in the bladder cancer tissues when compared with that in the paracancerous tissues. shRNA YAP inhibited cell proliferation, induced cell cycle arrest at G1 phase, and induced cell apoptosis. In conclusion, our findings provided the first evidence that YAP knockdown could inhibit cell proliferation and induce cell apoptosis of bladder cancer cells. YAP inhibition may be beneficial in the treatment of bladder cancer.
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Barrett-Bergshoeff, Marrie, Femke Noorman, Rogier Bos, and Dingeman C. Rijken. "Monoclonal Antibodies against the Human Mannose Receptor that Inhibit the Binding of Tissue-type Plasminogen Activator." Thrombosis and Haemostasis 77, no. 04 (1997): 718–24. http://dx.doi.org/10.1055/s-0038-1656040.
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SummaryTo study the role of the mannose receptor in cellular uptake and degradation of tissue-type plasminogen activator (t-PA), a set of five monoclonal antibodies (Moab) was generated against the mannose receptor isolated from human placental tissue.All Moab specifically recognised the 175 kDa mannose receptor in a crude placenta extract, as shown in Western blot analysis. By use of im- munohistochemistry, we showed that in human placenta only the Hof- bauer cells (fetal macrophages) express the mannose receptor. Epitope competition experiments indicated that the Moab bound to at least two different epitopes on the receptor molecule. Moab 14-3, 14-5, and 15-2, which are directed against one of these epitopes, strongly inhibited the interaction between the purified mannose receptor and t-PA. These Moab also inhibited mannose receptor-mediated degradation of t-PA by cultured human macrophages. The low density lipoprotein receptor-related protein (LRP) mediated t-PA degradation was not affected by the Moab.It is concluded that the Moab are useful for studying the expression of the human mannose receptor in Western blot and in immunohisto-chemistry, and for studying the interactions between the human mannose receptor and the mannose-containing ligand t-PA.
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Yu, J. "Elastic tissues of the intervertebral disc." Biochemical Society Transactions 30, no. 6 (November 1, 2002): 848–52. http://dx.doi.org/10.1042/bst0300848.
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Elastic fibres have been generally considered to play no significant role in the mechanical functioning of the intervertebral disc since earlier studies reported that the elastic fibre network was sparse and irregular. However, a recent study has reported that the network is highly organized and that the distribution and orientation of elastic fibres varies from region to region. In the annulus, elastic fibres appear densely distributed in the region between the lamellae and also in ‘bridges’ across the lamellae. They are also organized in the nucleus where long straight fibres are radially oriented and anchor perpendicularly or obliquely into the cartilaginous endplate. Immunohisto-chemistry using specific antibodies indicates that elastin is present in the network, as is fibrillin. Biochemical studies show, however, that the amino acid composition of the residue remaining after alkaline (NaOH) extraction or CNBr digestion contains a higher concentration of polar amino acids than ligamentum nuchal elastin. The composition of the residue suggests that disc elastin may cross-link strongly with some other matrix components. With such coupling, it is thought that elastic fibres could play a significant mechanical role even though overall elastin is less than 5% of the total dry weight of the disc.
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Harahap, Fadhlina, Hartono Tjahjadi, and Kusmardi Kusmardi. "The potential of programmed death ligand-1 expression in ovarian malignant germ cell tumors as a prognostic factor." Revista Romana de Medicina de Laborator 28, no. 4 (October 1, 2020): 393–403. http://dx.doi.org/10.2478/rrlm-2020-0032.
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Abstract Background: Ovarian malignant germ cell tumors (OMGCT) that fail to recover with conventional management have a poor prognosis. Several recurrent events after chemotherapy have been found. Programmed death ligand-1 (PD-L1) is expressed in various malignancies and tumor infiltrating lymphocytes (TILs) with a known role as a prognostic factor. Objective: To determine the role of PD-L1 expression in OMGCT in determining overall survival (OS) and progression-free survival (PFS). Methods: Expression of PD-L1 was assessed from PD-L1 immunohisto-chemistry in paraffin block preparations from 40 patients diagnosed with OMGCT who met the inclusion criteria. The relationship between clinicopathological characteristics and OS and PFS was analyzed using the Kaplan-Meier method and multivariate analysis using the Cox regression model. Results: No significant relationship was found between PD-L1 expression in tumor cells with 2-year OS (p=0.275) and PFS (p=0.421) in OMGCT. A significant association was found between histopathologic types with 2-year OS (p=0.002), and cancer stage with 2- year OS (p=0.028) and PFS (p=0.014). Conclusion: PD-L1 expression in tumor cells was not related to OS and PFS in OMGCT patients. There is a tendency for death and recurrence in patients OMGCTs with low PD-L1 expression in tumor cells.
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Tury, A., G. Mairet-Coello, F. Poncet, C. Jacquemard, P. Y. Risold, D. Fellmann, and B. Griffond. "QSOX sulfhydryl oxidase in rat adenohypophysis: localization and regulation by estrogens." Journal of Endocrinology 183, no. 2 (November 2004): 353–63. http://dx.doi.org/10.1677/joe.1.05842.
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The expression of the rat quiescin sulfhydryl oxidase (rQSOX) and its putative regulation by estrogens were investigated in the adenohypophysis. Immunohistochemical observations revealed that rQSOX protein is abundantly expressed throughout the anterior lobe of the pituitary, and can be found in almost all the different cell populations. However, as shown by double immunohisto-chemistry, the cells displaying the strongest rQSOX labeling belong to a subset of gonadotrophs. Immunoelectron microscopy showed that, in adenohypophyseal cells, the protein is linked to the membranes of the rough endoplasmic reticulum, the Golgi apparatus and to dense-core secretory granules. These results are consistent with the secretion of the protein and its presumed role in the extracellular matrix. According to its sulfhydryl oxidase function, rQSOX could also participate in the intracellular folding of secreted proteins or hormones like LH and FSH and act as an endogenous redox modulator of hormonal secretion. A semiquantitative RT-PCR analysis of rQSOX level across the estrous cycle and the fact that chronic administration of 17 β-estradiol to ovariectomized rats led to a sustained up-regulation of rQSOX in the pituitary suggest that rQSOX expression is controlled by sex hormone levels. Further investigations are needed in order to elucidate its precise roles in that gland and the mechanisms of its regulation.
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Ward, J. M., and W. Sheldon. "Expression of Mononuclear Phagocyte Antigens in Histiocytic Sarcoma of Mice." Veterinary Pathology 30, no. 6 (November 1993): 560–65. http://dx.doi.org/10.1177/030098589303000610.
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Twenty cases of histiocytic sarcoma in 15 female and five male (384 to 722 days of age) hybrid F1(C57BL/6 x BALB/c) or F2(F1 x F1) mice were studied for expression of mononuclear phagocyte and other antigens. Histiocytic sarcomas were found most often in liver, uterus, spleen, and lung. Tissues fixed in Bouin's fluid provided preservation of antigen immunoreactivity, using avidin biotin peroxidase complex immunohisto-chemistry, with monoclonal and polyclonal antibodies. The mononuclear phagocyte antigens, lysozyme and Mac-2 (a galactose-specific lectin that binds IgE), were found in 60-70% of the cases. The receptor for the macrophage colony-stimulating factor (CSF-1), c-fms, was expressed in 2/20 (10%) of the cases. Mouse immunoglobulins were not found in histiocytic sarcoma cells. In uterine histiocytic sarcomas, previously reported as Schwannomas because of their histologic appearance, S-100 protein was not expressed by tumor cells, although they usually expressed Mac-2 and lysozyme. Hyaline droplets were found in the renal tubules of only 2/19 cases. Our studies provide evidence that murine histiocytic sarcoma expresses antigens (Mac-2, lysozyme, c-fms) found in cells of the mononuclear phagocyte series, in contrast to the B-cell origin of many human histiocytic tumors.
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Shulman, K., S. Rosen, K. Tognazzi, E. J. Manseau, and L. F. Brown. "Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases." Journal of the American Society of Nephrology 7, no. 5 (May 1996): 661–66. http://dx.doi.org/10.1681/asn.v75661.
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Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a potent enhancer of microvascular permeability and a selective endothelial cell growth factor. In normal human kidney, VPF/VEGF mRNA and protein are strongly expressed by visceral glomerular epithelial cells, and VPF/VEGF may be an important regulator of glomerular endothelial cell function. This study examined 47 renal biopsies from patients with a variety of glomerular diseases for expression of VPF/VEGF mRNA and protein by in situ hybridization and immunohisto-chemistry. In many glomerular diseases, VPF/VEGF-expressing cells were decreased in number or absent in areas of focal or global glomerular sclerosis. Decreased numbers of VPF/VEGF-expressing cells in glomeruli were also noted in amyloidosis, diabetes, crescentic glomerulonephritis, and diffuse endocapillary proliferative glomerulonephritis associated with systemic lupus erythematosus. Normally, release of VPF/ VEGF must be under strict control because it is some 50,000 times more potent than histamine as an inducer of microvascular permeability. Damage to visceral epithelial cells in a variety of glomerular diseases has the potential for releasing relatively large amounts of VPF/VEGF locally, leading to increased glomerular permeability. In addition, because VPF/ VEGF is also an endothelial growth factor, the loss of normal, controlled secretion of VPF/VEGF after damage to visceral epithelial cells could lead to important alterations in glomerular endothelial cell function.
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Aan Setiawan, Mulawan Umar, and Erial Bahar. "Association Between Ki67 After Neoadjuvant Chemotherapy and Disease-Free Survival in Breast Cancer." Sriwijaya Journal of Surgery 4, no. 2 (May 25, 2021): 219–39. http://dx.doi.org/10.37275/sjs.v4i2.57.
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Background: Post Chemotherapy Ki67 in recent year has been investigated as a predictive and prognostic factor in locally advanced breast cancer patient undergoing neoadjuvant chemotherapy.
Objectives: To describe the relationship between post-chemotherapy Ki67 and disease-free survival after neoadjuvant chemotherapy in patients with locally advanced breast cancer at Dr. Hospital. Mohammad Hoesin Palembang.
Methods: This study is an analytical observational study with prognostic test design conducted in 30 stage III B breast cancer patient. A retrospective search of a prospectively maintained clinical database was performed to identify patient treated with neoadjuvant chemotherapy at the Mohammad Hoesin Hospital. The expression of Ki67 was assessed using immunohisto-chemistry in post therapy surgical excision specimen.
Results: From 30 patients, there was a significant relationship between Post Chemotherapy Ki67 and disease- free survival in patients with locally advanced breast cancer (r = -0,742, p = 0.000). The cut off point value of Ki67 was 27,5% with an area under curve (AUC) of 0,716. The results of the post-chemotherapy Ki67 prognosis test included sensitivity 64%, specificity 60%, Positive Predictive Value 88,9%, Negative Predictive Value 25%, accuracy 63,3%.
Conclusion: There is a significant relationship between Post Chemotherapy Ki67 to disease free survival and Post Chemotherapy Ki67 can be used as a prognostic biomarker in breast carcinoma patients undergoing neoadjuvant chemotherapy.
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Hendrickx, A. G., N. Makori, and P. Peterson. "The nonhuman primate as a model of developmental immunotoxicity." Human & Experimental Toxicology 21, no. 9-10 (September 2002): 537–42. http://dx.doi.org/10.1191/0960327102ht294oa.
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Macaques are well suited for preclinical testing of biopharmaceutics due to reproductive and developmental similarities with humans. In order to characterize ontogeny of the immune system in this model, we studied lymphocyte and antigen-presenting cell populations in developing lymphoid tissues of rhesus macaque fetuses during the second and third trimesters [gestation days (GD) 75–145, term 165 days]. Systemic lymphoid tissues (thymus, spleen and lymph nodes, and intestinal tissue) were examined for morphology and cell surface markers by immunohisto-chemistry. Lymphocytes were further characterized by flow cytometry for differentiation markers. Splenic tissue from early second trimester fetuses was populated mainly by CD20+ B cells while the thymus contained large numbers of CD3+ T cells. In the late second trimester (day 80), appro-ximately equal populations of B and T cells were present in both tissues and numerous dendritic cells (p55+) were present in the intestinal lamina propria. By the second trimester, the rhesus macaque fetal lymphoid system is well developed. Analysis of lymphoid organs from retinoic acid-treated fetuses indicated that the T-cell (thymus)-dependent compartment of the spleen white pulp in specimens with thymic aplasia showed a reduction in size and proportion of CD3+ T cells compared to controls. Our findings indicate that RA-induced thymic defects result in disrupted development of the splenic T-cell-dependent compartment.
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Mathioudaki, Konstantina, Panagiotis Prezas, Dimitra Alexopoulou, Eleftherios Diamandis, Dimitris Xynopoulos, Alexandros Ardavanis, Niki Arnogiannaki, Andreas Scorilas, and Maroulio Talieri. "Clinical significance of kallikrein-related peptidase 7 (KLK7) in colorectal cancer." Thrombosis and Haemostasis 101, no. 04 (2009): 741–47. http://dx.doi.org/10.1160/th08-07-0471.
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SummaryHuman tissue kallikrein-related peptidases are a family of 15 secreted serine proteases, located at chromosome 19q13.4. Most of them have been reported to be potential biomarkers for several carcinomas and other diseases. Human tissue kallikrein-related peptidase 7 (KLK7) has been purified from human stratum corneum and resembles a chymotryptic endopeptidase originally called stratum corneum chymotryptic enzyme (SCCE). In this study, we examined for the first time, the prognostic value of KLK7 mRNA expression, using a semi-quantitative RT-PCR method, in 105 colorectal cancer tissues for 54 of which, paired normal colonic mucosa were available. Furthermore, we analysed the expression of KLK7 in 10 adenomas, in 18 biopsies of inflamed colon mucosa, as well as in 22 human cancer cell lines of various origin, four of them being of colon. A defined number of colon cancer samples were also examined by immunohisto-chemistry. KLK7 expression was higher in cancerous than in normal tissues. Less differentiated tumors of more advanced stage showed higher KLK7 expression. Follow-up analysis revealed that KLK7 was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). In addition, selected colon cancer samples highly expressing KLK7 gene, showed intense immunohistochemical staining for KLK7, enhancing RTPCR results. Present data suggest that KLK7 gene is up-regulated in colon cancer and its expression predicts poor prognosis for colon cancer patients.
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Sharma, Sarita, Jyoti Sarah A. Khater, Eman Abd ElHakim, Basma Emad Aboulhoda, Laila Ahmed Rashed, and Ezz El Din Shalaby. "Evaluation of role of gapdh, gsk-3, b-catenin, dna fragmentation and immunohisto chemistry of caspase 3 in estimation of post mortem interval in albino rats." International Journal of Medical Toxicology & Legal Medicine 23, no. 1and2 (2020): 176. http://dx.doi.org/10.5958/0974-4614.2020.00028.5.
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Ye, Sheng, Jian Rong, Xiaohong Fu, and Tongyu Lin. "Clinical significance of Fas, VEGF, and EGFR expression in advanced gastric carcinoma." Journal of Clinical Oncology 31, no. 4_suppl (February 1, 2013): 58. http://dx.doi.org/10.1200/jco.2013.31.4_suppl.58.
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58 Background: Researches had proved that apoptotic signal proteins Fas-mediated cellular apoptosis influenced development of gastric carcinoma and affected survival of gastric carcinoma patients. Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) over expression had been associated with poor survival in several cancers including gastric carcinoma. Methods: Immunohisto-chemistry was performed to detect Fas, EGFR and VEGF protein expression in 60 newly diagnosed patients with gastric carcinoma in the First Affiliated Hospital of Sun Yat-sen University from November 1999 to June 2005. Clinical Data of these patients were reviewed. Time to progression (TTP) and overall survival (OS) were compared by log-rank test according to the expression status of Fas, EGFR and VEGF. Results: There were 40 males and 20 females, all patients were stage IV. All patients were treated with infused fluorouracil plus leucovorin and oxaliplatin or paclitaxel. The positive rate of Fas, EGFR and VEGF in gastric carcinoma was 73.3%, 35% and 40% respectively. TTP for patients with Fas positive was significantly superior to patients with Fas-negative (p<0.05). EGFR and VEGF were not correlated with TTP (p>0.05). Fas, EGFR and VEGF were not associated with overall survival(p>0.05). Conclusions: Fas, EGFR and VEGF are often expressed in gastric carcinoma. Fas expression is correlated with longer TTP. EGFR and VEGF expression were not associated with TTP. Fas, EGFR and VEGF were not a prognostic factor for OS.
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Mallick, Debjani, Sayan Kundu, Sudipta Chakrabarti, and Prosun Gayen. "The Significant Impact of Immunohistochemistry in the Classification of Lung Carcinoma on Small Biopsies." PERSPECTIVES IN MEDICAL RESEARCH 8, no. 3 (April 6, 2021): 60–65. http://dx.doi.org/10.47799/pimr.0803.13.
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Background : There are limitations of histomorphology in the appropriate categorization of lung carcinoma where immunohistochemistry can confirm the morphological diagnosis and may add value in the poorly differentiated and undifferentiated tumors. The aim of the study was to assess the role of immunohistochemistry in classifying lung carcinoma on small biopsy samples. Methods and Material: A retrospective hospital based, observational study was conducted on cases of lung carcinoma diagnosed by core needle or bronchoscopic biopsies over a 3- year period. After evaluation of clinical findings and H&E sections, all biopsies were evaluated by immunohistochemical staining. The immunohistochemistry panel included cytokeratin cocktail, CK7, CK 20, TTF1, Napsin A, CK5/6, p40, synaptophysin, chromogranin, CD 56. Result: Out of 78 cases, the mean age was 58 +/- 11 years. Most prevalent malignancy type was adenocarcinoma (30, 38.1%). Adenocarcinoma cases were positive for CK7 (25/26, 96%), Napsin A (24/26, 92%), TTF1 (15/30, 50%) and negative for CK 20. Squamous cell carcinoma cases showed positivity for p40(18/22, 82%) and CK 5/6 (17/22.71%).Small cell carcinoma showed positivity for neuroendocrine markers synaptophysin (5/7,71%) and chromogranin(4/7, 57%) and CD 56 (6/7cases (85%).88% of small cell carcinomas,75% of adenocarcinomas and 72 % of squamous cell carcinomas were accurately diagnosed by morphology. Morphologic prediction was poor in the NSCC NOS group (0%) and poorly differentiated carcinomas (64%), which were finally, diagnosed by immunohistochemistry.In the morphologically diagnosed cases, immunohistochemistry confirmed the diagnosis. Conclusion: Thus, morphology added with immunohisto chemistry provides a crisp diagnosis thereby improving therapeutic efficacy
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Fratticci, A., F. A. Grieco, C. Spilioti, F. Giangaspero, L. Ventura, V. Esposito, M. Piccirilli, et al. "Differential expression of neurogenins and NeuroD1 in human pituitary tumours." Journal of Endocrinology 194, no. 3 (September 2007): 475–84. http://dx.doi.org/10.1677/joe-07-0020.
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Basic helix-loop-helix (bHLH) transcription factors are involved in neuroendocrine cell growth and differentiation. Though NeuroD1 is viewed as corticotroph specific, its overexpression in non-corticotroph pituitary adenomas (PAs) may reflect the activation of molecular pathways involving other bHLH factors, like neurogenins. To search for neurogenin–NeuroD1 molecular pathways in the human normal and tumoural pituitary. Fifty-one PAs – 22 clinically non-secreting (CNS) and 29 secreting respectively – and normal human pituitaries (NP) were studied for NeuroD1 and neurogenins (Ngn1, Ngn2 and Ngn3) gene expression by RT-PCR and quantitative real-time RT-PCR (qRT-PCR). Immunohisto-chemistry for Ngn2/3 was performed in some cases. NeuroD1, Ngn2, Ngn3 and Ngn1 were observed in up to 84.3, 76.5, 30.4 and 9.1% of PA respectively, only NeuroD1 and Ngn2 being frequently overexpressed when compared with NP. Whereas NeuroD1 expression was higher in corticotroph and CNS adenomas (P=0.0001 versus Pit-1-dependent PA), Ngn2 expression was higher in secreting PA, especially in Pit-1-dependent PA (P=0.007 and P=0.0006 versus CNS respectively). Pit-1-dependent PAwhich received pre-operative pharmacological treatment expressed higher Ngn2 levels than untreated cases (P=0.025). Nuclear Ngn2 was observed in NP and in most PA, especially ACTH- and GH-secreting adenomas. Nuclear Ngn3 was observed in a minority of secreting PA. Ngn2 is normally expressed in the anterior pituitary and frequently expressed in PA, but does not account for NeuroD1 overexpression where present. Owing to their low and inconstant expression, the biological significance of Ngn1/3 in the adult pituitary is uncertain.
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Olaniyi, M. O., O. L. Ajayi, O. O. Alaka, O. A. Mustapha, C. C. Brown, J. P. Shields, M. B. Ard, and T. Nagy. "Immunohistochemical and Ultrastructural Studies of Mycoplasma hyopneumoniae Strain in Naturally Infected Pigs in Nigeria." Folia Veterinaria 64, no. 1 (March 1, 2020): 1–10. http://dx.doi.org/10.2478/fv-2020-0001.
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AbstractEnzootic pneumonia caused by hyopneumoniae (MHYO) remains a serious concern to the swine industry in many countries including Nigeria. MHYO strains isolated from pigs from different countries and geographical locations are known to vary in pathogenicity. There is a paucity of information on the pathogenicity of the MHYO strain affecting pigs in Nigeria. This study investigated the pathogenicity of the MHYO strain in naturally infected pigs using immunohisto-chemistry and electron microscopy. Two hundred and sixty four lungs of slaughtered pigs were randomly collected from abattoirs at Abeokuta, Ibadan and Lagos, in Southwest Nigeria. A sub-sample of 104 pneumonic and 20 apparently normal lungs was selected, processed for routine histopathological examination and immunohistochemistry, while 3 lung tissues samples were selected for ultrastructural studies. The most significant microscopic changes observed were suppurative broncho-interstitial pneumonia associated with varying degrees of lymphoid hyperplasia of the bronchus-associated lymphoid tissue (BALT) and thickened alveolar septa due to cellular infiltration consisting predominantly of neutrophils and a few mononuclear cells. Immunohistochemically, MHYO antigen was detected in 86/104 (82.69 %) of MHYO-infected lung tissues and typically exhibited a granular brown reaction on the bronchial and bronchiolar epithelial lining, mononuclear cells in the BALT and luminal cellular exudates within the airways. Transmission electron microscopy revealed numerous Mycoplasma organisms in the lumina of the airways, in between degenerated cilia, while a few Mycoplasmas were located within the alveoli. It was concluded that the MHYO strain detected in this study was pathogenic to pigs and capable of inducing pneumonia, and therefore implicated in the pathogenesis.
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Eiam-Ong, Somchit, Mookda Chaipipat, Krissanapong Manotham, and Somchai Eiam-Ong. "Aldosterone rapidly activates p-PKC delta and GPR30 but suppresses p-PKC epsilon protein levels in rat kidney." Endocrine Regulations 53, no. 3 (July 1, 2019): 154–64. http://dx.doi.org/10.2478/enr-2019-0016.
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AbstractObjectives. Aldosterone rapidly enhances protein kinase C (PKC) alpha and beta1 proteins in the rat kidney. The G protein-coupled receptor 30 (GPR30)-mediated PKC pathway is involved in the inhibition of the potassium channel in HEK-239 cells. GPR30 mediates rapid actions of aldosterone in vitro. There are no reports available regarding the aldosterone action on other PKC isoforms and GPR30 proteins in vivo. The aim of the present study was to examine rapid actions of aldosterone on protein levels of phosphorylated PKC (p-PKC) delta, p-PKC epsilon, and GPR30 simultaneously in the rat kidney.Methods. Male Wistar rats were intraperitoneally injected with normal saline solution or aldosterone (150 µg/kg body weight). After 30 minutes, abundance and immunoreactivity of p-PKC delta, p-PKC epsilon, and GPR30 were determined by Western blot analysis and immunohisto-chemistry, respectively.Results. Aldosterone administration significantly increased the renal protein abundance of p-PKC delta by 80% (p<0.01) and decreased p-PKC epsilon protein by 50% (p<0.05). Aldosterone injection enhanced protein immunoreactivity of p-PKC delta but suppressed p-PKC epsilon protein intensity in both kidney cortex and medulla. Protein abundance of GPR30 was elevated by aldosterone treatment (p<0.05), whereas the immunoreactivity was obviously changed in the kidney cortex and inner medulla. Aldosterone translocated p-PKC delta and GPR30 proteins to the brush border membrane of proximal convoluted tubules.Conclusions. This is the first in vivo study simultaneously demonstrating that aldosterone administration rapidly elevates protein abundance of p-PKC delta and GPR30, while p-PKC epsilon protein is suppressed in rat kidney. The stimulation of p-PKC delta protein levels by aldosterone may be involved in the activation of GPR30.
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Barnes, Maria J., Karen Lapanowski, Jose A. Rafols, David M. Lawson, and Joseph C. Dunbar. "Chronic Nitric Oxide Deficiency is Associated with Altered Leutinizing Hormone and Follicle-Stimulating Hormone Release in Ovariectomized Rats1." Experimental Biology and Medicine 227, no. 9 (October 2002): 817–22. http://dx.doi.org/10.1177/153537020222700915.
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Nitric oxide (NO) synthase (NOS) has been found in the gonadotrophs and folliculo-stellate cells of the anterior pituitary. Previous observations from our laboratory suggest that NO may play a role in regulating gonadotropin secretion. Because estrogen secretion by the ovary can influence gonadotropin secretion, we investigated the hypothesis that chronic in vivo NO deficiency has a direct estrogen-independent effect on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Chronic NO deficiency was induced by adding an NOS inhibitor, N-nitro-L-arginine (L-NNA, 0.6 g/l) to the drinking water of ovariectomized (OVX) rats. The control OVX rats were untreated. After 6–8 weeks, the animals were sacrificed, and the pituitaries were removed and perfused continuously for 4 hr in the presence of pulsatile gonadotropin-releasing hormone (GnRH, 500 ng/pulse) every 30 min. S-Nitroso-l-acetyl penicillamine (SNAP, an NO donor, 0.1 mM) or l-nitro-arginine methyl ester (L-NAME, an NOS inhibitor, 0.1 mM) was added to the media and perfusate samples were collected at 10-min intervals. GnRH-stimulated LH and FSH levels were significantly lower in pituitaries from OVX/NO-deficient pituitaries compared with pituitaries from the OVX control group. The addition of SNAP significantly decreased LH and FSH secretion by pituitaries from OVX control animals, but significantly increased their secretion by pituitaries from the OVX/NO-deficient animals. L-NAME also suppressed LH and FSH secretion by pituitaries from the OVX control animals and stimulated their release by pituitaries from the NO-deficient/OVX animals. Immunohisto-chemistry of frontal sections through the hypothalamus demonstrated that OVX/NO deficiency is associated with increased GnRH in the median eminence. We conclude that NO has a chronic stimulatory effect on LH and FSH release and the subsequent altered secretory responsiveness to NO agonist or antagonist is the result of chronic NO suppression.
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Liu, Wei-Wei, Zong-Yuan Zeng, Qiu-Liang Wu, Jing-Hui Hou, and Yi-Yong Chen. "Overexpression of MMP-2 in laryngeal squamous cell carcinoma: A potential indicator for poor prognosis." Otolaryngology–Head and Neck Surgery 132, no. 3 (March 2005): 395–400. http://dx.doi.org/10.1016/j.otohns.2004.09.050.
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OBJECTIVES: To investigate the expression and clinical significance of gelatinases (MMP-2 and MMP-9) in patients with laryngeal squamous cell carcinoma (LSCC). STUDY DESIGN AND SETTING: In a retrospective study of 72 consecutive patients with LSCC hospitalized in a single cancer center, immunohisto-chemistry was used to examine the expression of MMP-2 and MMP-9 in surgical samples. The results were compared to clinicopathological features and prognosis. RESULTS: The positive expression of MMP-2 and MMP-9 in patients with LSCC was 50% (36/72) and 73.6% (53/72), respectively. According to the expression scale, there were 36 patients of -, 26 patients of +, 7 patients of + +, and 3 patients of + + + expression of MMP-2; 19 patients of -, 26 patients of +,16 patients of ++, and 11 patients of + + + expression of MMP-9. There was no significant relationship found between the expression of MMP-2 or MMP-9 and clinicopathological features of LSCC, such as histological grade, primary site, T stage, N stage, and clinical stage. The 5-year overall survival (OS) and disease-free survival (DFS) rate calculated by Kaplan-Meier method in patients with negative and positive expression of MMP-9 and MMP-2 was 73.68%, 50.94%, 73.68%, and 49.06% in MMP-9 and 72.22%, 41.67%, 72.22%, and 38.89% in MMP-2, respectively. Significant 5-year survival difference was found between patients with negative and positive expression of MMP-2 (log rank = 6.74, P = 0.0094). There was significant lower survival rate in patients with higher positive expression of MMP-2 (log rank = 11.77, P = 0.0028). In glottic laryngeal cancer, positive expression of MMP-2 could predict poor survival and was more likely to present primary recurrence. CONCLUSION: The expression of MMP-2 could be used as a potential predictor for poor prognosis in patients with LSCC.
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Ismail, Soheir S., Amr L. Farag, Diaa Eldin M. Sherif, and Ibrahim S. Alhussini. "Evaluation of the Prognostic Value of Ki-67 in Early Stage Breast Cancer." Tumori Journal 107, no. 1_suppl (May 26, 2021): 15. http://dx.doi.org/10.1177/03008916211016798.
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Background: Breast cancer is a disease which have a variety of important features whose different phenotype only partially summarize the underlying biological complexity. Treatment choices in routine management principally rely on the clinical and pathological characteristics of the disease, although molecular classification currently offers information alongside that provided by clinical and pathological examination. The decision to offer adjuvant chemotherapy to patients is not easy and the knowledge of prognostic factors is mandatory. Ki 67 plays an important role in this context, especially in patients who do not have access to genetic signatures. Aim of the work: This study aims to evaluate the value of Ki67 as a prognostic factor in relation to disease free survival and other clinico-pathological factors in Egyptian females with early stage breast cancer. Patients and Methods: Type of study: This is a retrospective cohort study. Study population: It consisted of 124 patients diagnosed with early stage breast cancer. Study Period: They were diagnosed between January 2011 and December 2015. Study setting: The patients were following up in Ain Shams University Hospital clinical oncology department. Information were manually retrieved from the records of the clinical oncology department at Ain Shams university hospitals. Clinical and pathological tumor characteristics were collected using patient charts and pathology reports. Results: Our study showed a significant relation between Ki67 index and estrogen receptors, progesterone receptors and Her2 neu status. Ki67 was found to be statistically significantly correlated to intrinsic subtypes. Our study was unable to find out the effect of Ki67 on disease free survival. Cox regression analysis revealed a statistical significant influence of estrogen receptors status on disease free survival. It also revealed statistical prognostic effect of progesterone receptors and Her2 status on disease free survival. Covariate analysis of results in our study showed that tumor with T4 stage has a significant prognostic effect on disease free survival. Conclusion: ki67 index may have a prognostic role in management of early stage breast cancer in relation to other prognostic markers like hormone receptor status and HER2neu expression. Moreover, immunohisto-chemistry-based subtyping is extremely important to classify breast carcinoma into molecular subtypes that vary in clinic-pathological features and would lead to different prognosis. Thus, molecular subtyping is essential for breast carcinoma management.
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Mahadevan, Daruka, Catherine Spier, Kimiko Della Croce, Susan Miller, Benjamin George, Christopher J. Riley, Stephen Warner, Thomas M. Grogan, and Thomas P. Miller. "Gene Expression Profiling of Peripheral T-Cell Lymphoma (PTCL, NOS) and Comparison to Diffuse Large B-Cell Lymphoma (DLBCL)." Blood 104, no. 11 (November 16, 2004): 2277. http://dx.doi.org/10.1182/blood.v104.11.2277.2277.
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Abstract Background: WHO classifies NHL into B (~85%) and T (~15%) cell subtypes. Of the T-cell NHL, peripheral T-cell NHL (PTCL, NOS) comprises ~6–10% with an inferior response and survival to chemotherapy compared to DLBCL. Gene Expression Profiling (GEP) of DLBCL has provided molecular signatures that define 3 subclasses with distinct survival rates. The current study analyzed transcript profiling in PTCL (NOS) and compared and contrasted it to GEP of DLBCL. Methods : Snap frozen samples of 5 patients with PTCL (NOS) and 4 patients with DLBCL were analyzed utilizing the HG-U133A 2.0 Affymetrix array (~18,400 transcripts, 22,000 probe sets) after isolating and purifying total RNA (Qiagen, RNAeasy). The control RNA samples were isolated from normal peripheral blood (PB) B-cell (AllCell, CA), normal PB T-cell (AllCell, CA) and normal lymph node (LN). Immunohisto-chemistry (IHC) confirmed tumor lineage and quantitative real time RT-PCR was performed on selected genes to validate the microarray study. The GEP data were processed and analyzed utilizing Affymetrix MAS 5.0 and GeneSpring 5.0 software. Our data were analyzed in the light of the published GEP of DLBCL (lymphochip and affymtrix) and the validated 10 prognostic genes (by IHC and real time RT-PCR). Results : Data are represented as “robust” increases or decreases of relative gene expression common to all 5 PTCL or 4 DLBCL patients respectively. The table shows the 5 most over-expressed genes in PTCL or DLBCL compared to normal T-cell (NT), B-cell (NB) and lymph node (LN). PTCL vs NT PTCL vs LN DLVCL vs NB DLBCL vs LN COL1A1 CHI3L1 CCL18 CCL18 CCL18 CCL18 VNN1 IGJ CXCL13 CCL5 UBD VNN1 IGFBP7 SH2D1A LYZ CD52 RARRES1 NKG7 CCL5 MAP4K1 Of the top 20 increases, 3 genes were common to PTCL and DLBCL when compared to normal T and B cells, while 11 were common when compared to normal LN. Comparison of genes common to normal B-cell and LN Vs DLBCL or PTCL and normal T-cell and LN Vs PTCL or DLBCL identified sets of genes that are commonly and differentially expressed in PTCL and/or DLBCL. The 4 DLBCL patients analyzed express 3 of 10 prognostic genes compared to normal B-cells and 7 of 10 prognostic genes compared to normal LN and fall into the non-germinal center subtype. Quantitative real time RT-PCR on 10 functionally distinct common over-expressed genes in the 5 PTCL (NOS) patients (Lumican, CCL18, CD14, CD54, CD106, CD163, α-PDGFR, HCK, ABCA1 and Tumor endothelial marker 6) validated the microarray data. Conclusions: GEP of PTCL (NOS) and DLBCL in combination with quantitative real time RT-PCR and IHC have identified a ‘molecular signature’ for PTCL and DLBCL based on a comparison to normal (B-cell, T-cell and LN) tissue. The categorization of the GEP based on the six hallmarks of cancer identifies a ‘tumor profile signature’ for PTCL and DLBCL and a number of novel targets for therapeutic intervention.
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Trevisan, Brady, Martin Rodriguez, Jacqueline Dizon, Sunil George, Jordan E. Shields, Shannon Lankford, Rebecca Combs, et al. "Administration of FVIII-Expressing Human Placental Cells to Juvenile Sheep Yields Multi-Organ Engraftment, Therapeutic Plasma FVIII Levels and Alter Immune Signaling Pathways to Evade FVIII Inhibitor Induction." Blood 138, Supplement 1 (November 5, 2021): 3966. http://dx.doi.org/10.1182/blood-2021-151207.
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Abstract We have previously reported that normal juvenile sheep that received weekly intravenous (IV) infusions of human (n=3) or an expression/secretion-optimized, bioengineered human/porcine hybrid (ET3) FVIII protein (n=3) for 5 weeks (20 IU/kg) developed anti-FVIII inhibitory antibodies (10-116 BU, and IgG titers of 1:20-1:245) by week 3 of infusion. By contrast, the IV infusion, or IP administration, of human placental mesenchymal cells (PLC) transduced with a lentiviral vector encoding a myeloid codon-optimized ET3 transgene (PLC-mcoET3) to produce high levels of ET3 protein (4.9-6IU/10^6 cells/24h) enabled the delivery of FVIII without eliciting antibodies, despite using PLC-mcoET3 doses that provided ~20-60 IU/kg ET3 each 24h to mirror the amount of FVIII protein infused. In addition, we showed that the route of PLC-mcoET3 administration (IP vs IV) did not impact the resultant plasma FVIII levels, with animals in these two groups exhibiting mean increases in FVIII activity (quantified by aPTT) of 30.9% and 34.2%, respectively, at week 15 post-treatment. Here, we investigated whether the sites and levels of PLC-mcoET3 engraftment were dependent upon the route of administration and performed s sheep-specific multiplexed transcriptomic analysis (NanoString) to define the immune signaling pathways that thwarted FVIII/ET3 protein immune response when ET3 was delivered through PLC. Tissue samples were collected from various organs at euthanasia and RT-qPCR performed using primers specific to the mcoET3 transgene, to the human housekeeping transcript GAPDH, and to sheep GAPDH, to quantify PLC-mcoET3 tissue engraftment, and normalize the results. RT-qPCR demonstrated PLC-mcoET3 engrafted, in both IP and IV groups, in all the organs evaluated (liver, lung, lymph nodes, thymus, and spleen). Animals that received PLC-mcoET3 via the IP route displayed higher overall levels of engraftment than their IV counterparts. The spleen was the preferential organ of engraftment for both IP and IV groups (IP:2.41±1.97%; IV: 0.64±0.54%). The IP group exhibited significantly higher engraftment in the left lobe of the liver (IP: 1.36±0.35%; IV: 0.041±0.022%), which was confirmed by immunohisto-chemistry (IHC) with an antibody to the human nuclear antigen Ku80 and ImageJ analysis (IP:5.24±3.36%; IV: 0±0). Of note is that the IP route resulted in higher levels of engraftment in the thymus, while IV infusion yielded higher levels of PLC-mcoET3 in lymph nodes. Analysis of H&E-stained tissues demonstrated they were devoid of any abnormal histologic changes and exhibited no evidence of hyperplasia or neoplasia, supporting the safety of the cell platform, irrespective of the route of administration. To date, NanoString analysis of PBMC collected at day 0, week 1, and week 5 post-infusion demonstrated that animals who received FVIII protein had upregulation of UBA5 and BATF, genes involved in antigen processing and Th17 signaling pathways, respectively. Although both IV and IP recipients of PLC-mcoET3 also had an increase in BATF, the IV group exhibited upregulation of BTLA, a gene involved in immune-tolerance, and downregulation of NOTCH and DDL1, involved in T cell differentiation, as well as MAPK12 and PLCG1, genes involved in proinflammatory cytokine regulation and T signaling within the Th17 signature. In IP recipients, BTLA, NOTCH, and DLL1 were all downregulated. Since ET3-reactive Th 1 cells were not present in any of the treated animals, it is possible that the Th17 cells are responsible for the inhibitory antibodies seen in the juvenile sheep treated with FVIII/ET3 protein, while in animals receiving PLC-mcoET3, downregulation of genes involved in T cell differentiation and proinflammatory cytokine signaling keeps the immune system in check to avoid an immune response. Disclosures Doering: Expression Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months. Spencer: Expression Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months.
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Li, Sung-Chou, Kuo-Chung Lan, Hsuan-Ning Hung, Wan-Ting Huang, Yun-Ju Lai, Hsin-Hsin Cheng, Chih-Chang Tsai, Kun-Long Huang, Huey-Ling You, and Te-Yao Hsu. "HSPA4 Is a Biomarker of Placenta Accreta and Enhances the Angiogenesis Ability of Vessel Endothelial Cells." International Journal of Molecular Sciences 23, no. 10 (May 19, 2022): 5682. http://dx.doi.org/10.3390/ijms23105682.
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Placenta accreta spectrum (PAS) accounts for 7% of maternal mortality and is associated with intraoperative and postoperative morbidity caused by massive blood loss, infection, and adjacent organ damage. The aims of this study were to identify the protein biomarkers of PAS and to further explore their pathogenetic roles in PAS. For this purpose, we collected five placentas from pregnant subjects with PAS complications and another five placentas from normal pregnancy (NP) cases. Then, we enriched protein samples by specifically isolating the trophoblast villous, deeply invading into the uterine muscle layer in the PAS patients. Next, fluorescence-based two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-TOF/MS were used to identify the proteins differentially abundant between PAS and NP placenta tissues. As a result, nineteen spots were determined as differentially abundant proteins, ten and nine of which were more abundant in PAS and NP placenta tissues, respectively. Then, specific validation with western blot assay and immunohisto/cytochemistry (IHC) assay confirmed that heat shock 70 kDa protein 4 (HSPA4) and chorionic somatomammotropin hormone (CSH) were PAS protein biomarkers. Further tube formation assays demonstrated that HSPA4 promoted the in vitro angiogenesis ability of vessel endothelial cells, which is consistent with the in vivo scenario of PAS complications. In this study, we not only identified PAS protein biomarkers but also connected the promoted angiogenesis with placenta invasion, investigating the pathogenetic mechanism of PAS.
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Garrido, Maritza P., Christopher Vallejos, Silvanna Girardi, Fernando Gabler, Alberto Selman, Fernanda López, Margarita Vega, and Carmen Romero. "NGF/TRKA Promotes ADAM17-Dependent Cleavage of P75 in Ovarian Cells: Elucidating a Pro-Tumoral Mechanism." International Journal of Molecular Sciences 23, no. 4 (February 15, 2022): 2124. http://dx.doi.org/10.3390/ijms23042124.
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Nerve growth factor (NGF) and its high-affinity receptor TRKA are overexpressed in epithelial ovarian cancer (EOC) displaying a crucial role in the disease progression. Otherwise, NGF interacts with its low-affinity receptor P75, activating pro-apoptotic pathways. In neurons, P75 could be cleaved by metalloproteinases (α and γ-secretases), leading to a decrease in P75 signaling. Therefore, this study aimed to evaluate whether the shedding of P75 occurs in EOC cells and whether NGF/TRKA could promote the cleavage of the P75 receptor. The immunodetection of the α-secretase, ADAM17, TRKA, P75, and P75 fragments was assessed by immunohisto/cytochemistry and Western blot in biopsies and ovarian cell lines. The TRKA and secretases’ inhibition was performed using specific inhibitors. The results show that P75 immunodetection decreased during EOC progression and was negatively correlated with the presence of TRKA in EOC biopsies. NGF/TRKA increases ADAM17 levels and the fragments of P75 in ovarian cells. This effect is abolished when cells are previously treated with ADAM17, γ-secretase, and TRKA inhibitors. These results indicate that NGF/TRKA promotes the shedding of P75, involving the activation of secretases such as ADAM17. Since ADAM17 has been proposed as a screening marker for early detection of EOC, our results contribute to understanding better the role of ADAM17 and NGF/TRKA in EOC pathogenesis, which includes the NGF/TRKA-mediated cleavage of P75.
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Rieu, Quentin, Antoine Bougoüin, Yvrick Zagar, Jonathan Chatagnon, Abdallah Hamieh, Julie Enderlin, Thierry Huby, and Emeline F. Nandrot. "Pleiotropic Roles of Scavenger Receptors in Circadian Retinal Phagocytosis: A New Function for Lysosomal SR-B2/LIMP-2 at the RPE Cell Surface." International Journal of Molecular Sciences 23, no. 7 (March 22, 2022): 3445. http://dx.doi.org/10.3390/ijms23073445.
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The retinal phagocytic machinery resembles the one used by macrophages to clear apoptotic cells. However, in the retina, the permanent contact between photoreceptor outer segments (POS) and retinal pigment epithelial (RPE) cells requires a tight control of this circadian machinery. In addition to the known receptors synchronizing POS internalization, several others are expressed by RPE cells. Notably, scavenger receptor CD36 has been shown to intervene in the internalization speed. We thus investigated members of the scavenger receptor family class A SR-AI and MARCO and class B CD36, SR-BI and SR-B2/LIMP-2 using immunoblotting, immunohisto- and immunocytochemistry, lipid raft flotation gradients, phagocytosis assays after siRNA/antibody inhibition, RT-qPCR and western blot analysis along the light:dark cycle. All receptors were expressed by RPE cell lines and tissues and colocalized with POS, except SR-BI. All receptors were associated with lipid rafts, and even more upon POS challenge. SR-B2/LIMP-2 inhibition suggested a role in the control of the internalization speed similar to CD36. In vivo, MARCO and CD36 displayed rhythmic gene and protein expression patterns concomitant with the phagocytic peak. Taken together, our results indicate that CD36 and SR-B2/LIMP-2 play a direct regulatory role in POS phagocytosis dynamics, while the others such as MARCO might participate in POS clearance by RPE cells either as co-receptors or via an indirect process.
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Couret, David, Cynthia Planesse, Jessica Patche, Nicolas Diotel, Brice Nativel, Steeve Bourane, and Olivier Meilhac. "Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions." Molecules 26, no. 21 (October 21, 2021): 6365. http://dx.doi.org/10.3390/molecules26216365.
Full textAbstract:
Introduction: The pleiotropic protective effects of high-density lipoproteins (HDLs) on cerebral ischemia have never been tested under acute hyperglycemic conditions. The aim of this study is to evaluate the potential neuroprotective effect of HDL intracarotid injection in a mouse model of middle cerebral artery occlusion (MCAO) under hyperglycemic conditions. Methods: Forty-two mice were randomized to receive either an intracarotid injection of HDLs or saline. Acute hyperglycemia was induced by an intraperitoneal injection of glucose (2.2 g/kg) 20 min before MCAO. Infarct size (2,3,5-triphenyltetrazolium chloride (TTC)-staining), blood–brain barrier leakage (IgG infiltration), and hemorrhagic changes (hemoglobin assay by ELISA and hemorrhagic transformation score) were analyzed 24 h post-stroke. Brain tissue inflammation (IL-6 by ELISA, neutrophil infiltration and myeloperoxidase by immunohisto-fluorescence) and apoptosis (caspase 3 activation) were also assessed. Results: Intraperitoneal D-glucose injection allowed HDL- and saline-treated groups to reach a blood glucose level of 300 mg/dl in the acute phase of cerebral ischemia. HDL injection did not significantly reduce mortality (19% versus 29% in the saline-injected group) or cerebral infarct size (p = 0.25). Hemorrhagic transformations and inflammation parameters were not different between the two groups. In addition, HDL did not inhibit apoptosis under acute hyperglycemic conditions. Conclusion: We observed a nonsignificant decrease in cerebral infarct size in the HDL group. The deleterious consequences of reperfusion such as hemorrhagic transformation or inflammation were not improved by HDL infusion. In acute hyperglycemia, HDLs are not potent enough to counteract the adverse effects of hyperglycemia. The addition of antioxidants to therapeutic HDLs could improve their neuroprotective capacity.
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Listiawan, M. Yulianto, Linda Astari, and Putri Hendria Wardhani. "Comparison amount of microphthalmia-associated transcription factor in vitiligo before and after narrowband-ultraviolet B therapy." Dermatology Reports, March 29, 2019. http://dx.doi.org/10.4081/dr.2019.8030.
Full textAbstract:
Vitiligo is the most commonly seen depigmentation disease with clinical manifestations of milk colored white macules, complex pathogenesis that is not well understood so that evolution of the disease is unpredictable and therapeutic outcomes are often unsatisfactory. Until now narrowband-ultraviolet B (NB-UVB) is considered the most effective and safe treatment for vitiligo. Therapy evaluation by looking at melanocytes function that can be seen with microphthalmia-associated transcription factor (MITF) immunohisto - chemistry will become more objective and accurate. This is a comparative analytic experimental study using pre-post test method comparing MITF in vitiligo patients before and after receiving NB-UVB conducted at Dr. Soetomo general hospital Surabaya, 12 vitiligo samples treated only with NB-UVB twice a week until 8 times therapies. The first exposure dose was 200 mJ and gradually increased 20% every therapy. Biopsy was performed before and after therapies and then MITF was compared. There was a significant difference between the amount of MITF in vitiligo before NB-UVB and after NB-UVB therapy stastistically, p=<0.001 (p=0.05). MITF is useful for indicators of treatment success.
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Li, G., X. Feng, and S. Wang. "Effects of Cu/Zn superoxide dismutase on strain injury-induced oxidative damage to skeletal muscle in rats." Physiological Research, 2005, 193–99. http://dx.doi.org/10.33549/physiolres.930614.
Full textAbstract:
This study was designed to determine whether the supplement of superoxide dismutase (SOD) could attenuate strain-induced oxidative damage to skeletal muscle in rats. Experimental animals were injured in right gastrocnemius muscles by a strain injury model. SOD-treated groups were given Cu/Zn SOD 10 000 U/kg body weight per day since injured, while control groups were given normal saline. Parameters of antioxidant and muscle damage were detected in plasma 3 and 7 days postinjury. The injured muscles were removed and fixed for histology observation and immunohisto-chemistry assay of desmin. The results showed that plasma levels of SOD, glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) in SOD group were significantly higher than in the saline group on day 3 or 7, while the plasma creatine kinase (CK) and malondialdehyde (MDA) were lower in the SOD group than in the saline group. The histological examination of muscle sections revealed a lower degree of damage in the SOD group in which the expression level of desmin was higher than in the saline group. It is suggested that SOD supplement may attenuate strain-induced muscle damage and facilitate its regeneration.
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Seyhan, Ekrem Cengiz, Sedat Altın, Erdogan Çetinkaya, Sinem Sökücü, Hülya Abalı, Nur Buyukpinarbasili, and Neslihan Fener. "Prognostic value of epidermal growth factor receptor expression in operable non-small cell lung carcinoma." Multidisciplinary Respiratory Medicine 5 (May 24, 2010). http://dx.doi.org/10.4081/mrm.2010.557.
Full textAbstract:
Background and aim: Increased expression of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC), supporting the tumor growth by a possible endocrine mechanism, affects patient survival negatively. We designed a study to test EGFR expression by immunohisto- chemistry (IHC) in resected stage I–II NSCLC and to correlate its overexpression with survival.
Methods: EGFR expression was evaluated in 98 consecutive NSCLC patients after complete resection (53 squamous cell carcinomas, 40 adenocarcinomas, 5 large cell carcinomas: stage I, 57 (58%) and stage II, 41 (42%). IHC was used to examine the expression of EGFR in resected lung tumor sam- ples obtained from these patients, who had no pre- or post- operative chemotherapy or radiotherapy. Univariate and multivariate analyses were performed for factors influencing patient survival.
Results: EGFR was expressed in 51 (52%) of 98 NSCLC sam- ples. More squamous tumors (61%) were EGFR-positive than adenocarcinomas (38%) (p = 0.038). There was a statistically significant correlation between EGFR expression and stage (p = 0.04). No difference was found between EGFR positive and negative tumors in the 5-year overall survival (57% vs. 73%, p = 0.13).
Conclusion: The level of EGFR expression in tumors was not a successful predictor of survival in resected NSCLC.
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Mentlein, Rolf, Kirsten Hattermann, Charles Hemion, Achim A. Jungbluth, and Janka Held-Feindt. "Expression and role of the cell surface protease seprase/fibroblast activation protein-α (FAP-α) in astroglial tumors." Biological Chemistry 392, no. 3 (March 1, 2011). http://dx.doi.org/10.1515/bc.2010.119.
Full textAbstract:
Abstract Seprase or fibroblast activation protein-α (FAP-α) is a cell-surface serine protease that was previously described nearly exclusively on reactive and tumor stromal fibroblasts and thought to be involved in tissue remodeling. We investigated the expression and significance of FAP-α in astrocytomas/glioblastomas. As shown by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohisto-chemistry, FAP-α was elevated in whole glioblastoma tissues and in particular in most glioma cells in situ and in vitro. In glioma stem-like cells (gliospheres), FAP-α was detected at low levels; however, FAP-α was considerably induced upon differentiation with 10% fetal calf serum. To explore its functional role, FAP-α was silenced by siRNA transfection. In Boyden chamber assays, FAP-α silenced cells migrated similar as control cells through non-coated or Matrigel (basal lamina)-coated porous membranes, but significantly slower through membranes coated with gelatin or brevican, a major component of brain extracellular matrix. Furthermore, FAP-α-silenced glioma cells migrated through murine brain slices much slower under the conditions tested than differentially fluorescent-labeled control cells. Thus, FAP-α is highly expressed on the surface of glioma cells and contributes to diffuse glioma invasion through extracellular matrix components.
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Iniguez, G., A. Villavicencio, F. Gabler, A. Palomino, and M. Vega. "Effect of nitric oxide on the expression of insulin-like growth factors and the insulin-like growth factor binding proteins throughout the lifespan of the human corpus luteum." Reproduction, December 1, 2001, 865–73. http://dx.doi.org/10.1530/rep.0.1220865.
Full textAbstract:
The presence of insulin-like growth factors (IGF), IGF binding proteins (IGFBP) and IGF receptor type 1 (IGF-IR) in the human corpus luteum was investigated by examining the expression and production of related proteins throughout the lifespan of the corpus luteum and the action of nitric oxide upon their production. The expression of proteins in corpora lutea from the early, mid-and late luteal phases was assessed by immunohisto-chemistry, evaluated by a semi-quantitative analysis and the functional study was performed in corpus luteum explants incubated with nitric oxide donors. IGF-I and -II and IGFBP-1 and -3 were measured in the culture media by specific immunoassays. The results showed that IGF-I and -II, IGFBP-1 to -6 and IGF-IR were detected in the human corpus luteum throughout the luteal phase. Moreover, the expression and production of IGF-I and IGFBP-1 increased progressively from corpora lutea from the early to late luteal phases (P < 0.05), whereas the expression and production of IGFBP-2, -4 and -5 were significantly higher in corpora lutea from the mid-luteal phase (P < 0.05). No differences were observed in the expression of IGF-II, IGFBP-3 and -6 and IGF-IR throughout the lifespan of the corpus luteum. However, functional studies showed that nitric oxide donors elicited a stimulatory action on production of IGF-I in corpora lutea from the early luteal phase (80%) and on production of IGFBP-1 in corpora lutea from the late luteal phase (50%) (P < 0.05), whereas production of IGF-II and IGFBP-3 was not affected by nitric oxide. In conclusion, the components of the IGF-IGFBP system are expressed in the human corpus luteum throughout its lifespan. Nitric oxide regulates IGF-I and IGFBP-1 production, indicating that the growth factors may serve, at least in part, as mediators of the action of nitric oxide in the human corpus luteum.
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Rzechorzek, Wojciech J., Brian K. Buckley, Kunji Hua, Daniel Pomp, Hua Zhang, and James E. Faber. "Abstract 222: Exercise Training Prevents Rarefaction of Pial Collaterals, Promotes Cerebral Arterial Remodeling, and Lessens Severity of Stroke in Aging Brain." Stroke 48, suppl_1 (February 2017). http://dx.doi.org/10.1161/str.48.suppl_1.222.
Full textAbstract:
Variation in anatomic extent of the collateral circulation is an important determinant of variation in the severity of ischemic stroke and efficacy of revascularization therapies. Yet pial collateral number and lumen diameter decrease with age, at least in mice. It is not known if this can be mitigated. We tested whether exercise training can accomplish this and if it also affects diameter of the posterior communicating collalterals (PComs) and primary cerebral arteries (ICA, BA, MCA, ACA, PCA). We randomized 30 male and 30 female, 12 months-old (~40 human years, hy) C57BL/6J mice to either sedentary or voluntary wheel-running (daily distance run was measured). At 25 mos-age (~70 hy), permanent MCA occlusion was followed 24h later by vascular casting after maximal dilation and by determination of infarct volume. Controls for aging were 3 mos-old sedentary mice (~16 hy). Training effect was confirmed by muscle fiber-type switching, body weight and cardiac hypertrophy (all p<0.05). Exercise prevented age-associated loss of collateral number and diameter (p=0.049 and 0.005, n=13-14) and reduced infarct volume by 50%, ie, to that seen in 3 months-old mice (p=0.01, n=7). Unlike pial collaterals, PCom diameter and number (ie, present bilaterally, unilaterally or absent) were unaffected by exercise. Of further interest, diameter of the primary cerebral arteries increased with aging alone (119 ± 1 vs 134 ± 5 μm averaged combined diameter, p=0.02, n=10-14); this effect tended to increase further with exercise (143 ± 4 μm, p=0.07, n=13). Mechanistically, exercise increased vascular expression (assessed by immunohisto-chemistry) of total eNOS (p=0.03, n=5-6), phospho-eNOS (p=0.004, n=5) and a marker of anti-oxidative stress (SOD, p=0.008, n=5-6; but not HO-1, p=0.40, n=6). It did not alter a marker of aging (p16, p=0.42, n=5); analysis of additional targets is underway. In conclusion, exercise training prevented age-induced rarefaction of pial collaterals and reduced infarct volume. In addition and unexpectedly, aging also caused outward remodeling of the primary cerebral arteries, and exercise training tended to further augment this. These benefits of regular aerobic exercise were associated with increased eNOS bioavailability and reduced oxidative stress.
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Graf, Kristof, Thore Dietrich, Christiane Schneemann, Kirstin Atrott, Philipp Stawowy, Dietrich Menssen, Jörg Willuda, and Eckart Fleck. "Abstract 1735: Targeted Application of Interleukin-2 Activates T-Lymphocytes and Reduces Plaque Formation." Circulation 118, suppl_18 (October 28, 2008). http://dx.doi.org/10.1161/circ.118.suppl_18.s_379-b.
Full textAbstract:
A newly developed fusion protein (L19-IL2) consisting of an anti-ED-B fibronectin single chain antibody and the cytokine interleukin-2 (IL2), is a potent antitumor agent for renal cell cancer. ED-B fibronectin (ED-B) is expressed in inflammatory plaque lesions. Preliminary studies suggested that delivering IL2 locally to atherosclerotic tissue seem to reduce plaque progression. Therefore we investigated the application of L19-Il2 on lesion formation in apoE-deficient mice (apoE −/− ). 6-month old apoE −/− , fed with high fat diet (n = 5/group) were injected intravenously L19-IL2 (4290IU/g bodyweight), with L19 (antibody alone), with the control fusion protein D1-IL2 (4290IU/g bodyweight) or NaCL (control) at day 1, 3 and 5 and were sacrificed at day 7. Plaque lesion formation was analyzed by histology, immunohisto-chemistry (Mac3 = macrophages, CD31; actin, human IL2, ED-B, CD25, CD4), morphometry of the aortic root and by Sudan stain of the thoracic aorta followed by densitometry. Macrophage, ED-B, CD4, CD25 (IL-2 receptor subunit) content was analysed after immunohistochemistry. Results: Treatment with L19-IL2, L19, and D1-IL2 did not affect bodyweight, survival of mice compared to control (NaCL). Serum levels for blood glucose, cholesterol, liver and cardiac enzymes, and troponin were not different between L19-IL2, L19, and NaCL. Cardiac histology was also unaffected. Human IL2 was only detectable in plaque lesions after L19-IL2, but not after L19 or D1-IL2 treatment. L19-IL2 application significantly reduced plaque lesion size in the aortic root (L19-Il2: 23.2 ± 1.7%, L19: 35.2 ± 1.2%, D1-IL2: 31.6 ± 3.0%, NaCL: 31.0 ± 3.2%, p < 0.01), plaque extension in the thoracic aorta (L19-Il2: 5.3 ± 0.7%, L19: 8.2 ± 0.4%, D1-IL2: 9.8 ± 1.0%, NaCL: 8.9 ± 1.2%, p < 0.01). Mac3 immunoreactivity was reduced under L19-IL2, whereas CD4 and CD25 were strongly increased compared to L19, D1-IL2 and NaCL treated groups. Conclusion: A fusion protein, which delivers human IL-2 into plaque lesions, induces T-lymphocyte activation, reduction of macrophages and a reduction in plaque growth. The present study suggests that local application of IL2 activates cellular mechanisms involving T-lymphocytes leading to a reduction of atherosclerotic disease.