scholarly journals Human Kallikrein 10 Expression in Normal Tissues by Immunohistochemistry

2002 ◽  
Vol 50 (9) ◽  
pp. 1247-1261 ◽  
Author(s):  
Constantina D. Petraki ◽  
Vassiliki N. Karavana ◽  
Liu-Ying Luo ◽  
Eleftherios P. Diamandis
Keyword(s):  
Leydig Cells ◽  
Biological Fluids ◽  
Human Tissues ◽  
Protein Levels ◽  
Normal Tissues ◽  
Tissue Extracts ◽  
Organ Specific ◽  
Normal Human ◽  
Neuroendocrine Organs ◽  
Mouse Antibody

The normal epithelial cell-specific 1 (NES1) gene (official name kallikrein gene 10, KLK10) was recently cloned and encodes for a putative secreted serine protease (human kallikrein 10, hK10). Several studies have confirmed that hK10 shares many similarities with the other kallikrein members at the DNA, mRNA, and protein levels. The enzyme was found in biological fluids, tissue extracts, and serum. Here we report the first detailed immunohistochemical (IHC) localization of hK10 in normal human tissues. We used the streptavidin-biotin method with two hK10-specific antibodies, a polyclonal rabbit and a monoclonal mouse antibody, developed in house. We analyzed 184 paraffin blocks from archival, current, and autopsy material, prepared from almost every normal human tissue. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. Previously, we reported the expression of another novel human kallikrein, hK6, by using similar techniques. The IHC expression of hK10 was generally cytoplasmic and not organ-specific. A variety of normal human tissues expressed the protein. Glandular epithelia constituted the main immunoexpression sites, with representative organs being the breast, prostate, kidney, epididymis, endometrium, fallopian tubes, gastrointestinal tract, bronchus, salivary glands, bile ducts, and gallbladder. The choroid plexus epithelium, the peripheral nerves, and some neuroendocrine organs (including the islets of Langerhans, cells of the adenohypophysis, the adrenal medulla, and Leydig cells) expressed the protein strongly and diffusely. The spermatic epithelium of the testis expressed the protein moderately. A characteristic immunostaining was observed in Hassall's corpuscles of the thymus, oxyphilic cells of the thyroid and parathyroid glands, and chondrocytes. Comparing these results with those of hK6, we observed that both kallikreins had a similar IHC expression pattern.

scholarly journals Human Kallikrein 13 Expression in Normal Tissues: An Immunohistochemical Study

2003 ◽  
Vol 51 (4) ◽  
pp. 493-501 ◽  
Author(s):  
Constantina D. Petraki ◽  
Vassiliki N. Karavana ◽  
Eleftherios P. Diamandis
Keyword(s):  
Nervous System ◽  
Human Tissue ◽  
Leydig Cells ◽  
Human Tissues ◽  
Primordial Follicles ◽  
Normal Tissues ◽  
Trophoblastic Cells ◽  
Endocrine Organs ◽  
The Central Nervous System ◽  
Normal Human

The human tissue kallikrein 13 gene (KLK13), encoding for hK13 protein, was recently cloned and characterized. Here we describe the immunohistochemical (IHC) localization of hK13 in normal human tissues and compare it with the expression of two other kallikreins, hK6 and hK10. We performed the streptavidin-biotin IHC method on 204 paraffin blocks from archival, current, and autopsy material prepared from almost every normal human tissue, using a polyclonal and a monoclonal hK13 antibody. The staining was cytoplasmic and both antibodies yielded similar results. The hK13 protein was revealed in a variety of tissues, mainly in glandular epithelia. Other epithelia that expressed hK13 included the urothelium, the spermatic epithelium, and the epithelium of the choroid plexus. hK13 was intensely immunoexpressed by some endocrine organs, such as the adenohypophysis, the thyroid gland, the parathyroid glands, the adrenal medulla, the Leydig cells of the testis, and the cells of the endocrine pancreas. Immunoreactivity was also observed in the primordial follicles, the corpus luteum, and sparse luteinized cells in the stroma of the ovary, the trophoblastic cells of the placenta, the Hassall's corpuscles of the thymus, and chondrocytes. Nerves and ganglia of the peripheral nervous system, and both neurons and glial cells in the central nervous system, were positive. In short, hK13 was expressed by many glandular epithelia, some endocrine organs, and some specialized epithelia and cells. Comparison of these data with hK6 and hK10 expression suggests that the three kallikreins have a similar IHC pattern in normal human tissues.

scholarly journals CLONAL GROWTH IN VITRO OF EPITHELIAL CELLS FROM NORMAL HUMAN TISSUES

1956 ◽  
Vol 104 (4) ◽  
pp. 615-628 ◽  
Author(s):  
Philip I. Marcus ◽  
Steven J. Cieciura ◽  
Theodore T. Puck
Keyword(s):  
Hela Cell ◽  
Single Cells ◽  
Cross Sectional Area ◽  
Plating Efficiency ◽  
Human Tissues ◽  
Sectional Area ◽  
Nutrient Media ◽  
Cross Sectional ◽  
Normal Tissues ◽  
Normal Human

Tissue culture strains of cells from four different normal human tissues—liver, conjunctiva, kidney, and appendix—have been grown by the plating procedure previously developed for the HeLa strain of cervical carcinoma cells. This technique results in colony formation from isolated single cells, in a manner completely analogous to the plating of bacteria in semisolid nutrient media. Clonal cell strains have been isolated from each cell type. All behaved exactly alike in all properties studied except that some differences in plating efficiency were displayed in some of the growth media employed. The cells from normal human tissues resembled the HeLa S3 carcinomatous cell in the following properties:— (a) Single cells displayed a plating efficiency close to 100 per cent in an appropriate medium. (b) They all grew as an epithelial sheet on glass, the cells being closely packed and polygonal in shape. (c) They had mean generation times of 20 to 23 hours in the nutrient media employed, (d) The mitotic frequency was constant, and therefore the duration of mitosis was the same for all the strains studied, (e) The incidence of multinuclearity and giant formation was very low and similar in both types of cells. (f) Both classes of cells had the same total volume, and the same nuclear cross-sectional area. (g) Both also showed a tendency to spread more in the presence of human serum (concentration of 20 per cent or more) than in porcine serum. However, this differential morphological response was much more marked in the HeLa cell than in those from normal tissues. The only difference noted in the behavior of these two groups of cells lay in the tendency of the cells from normal tissues always to exhibit a greater cross-sectional area when spread on glass than the HeLa cell in the same medium. The frequency of occurrence of different types of multinuclearity in the HeLa cell and cells from normal tissues has been measured. The data suggest that multinuclearity depends on two factors: a necessary, predisposing state in the cell, and a random, independent event causing the appearance of an additional nucleus in such a prepared cell.

Oncofoetal antigens of human trophoblast

1979 ◽  
Vol 206 (1163) ◽  
pp. 163-182 ◽  
Keyword(s):  
Cell Lines ◽  
Transformed Cells ◽  
Igg Antibody ◽  
Human Trophoblast ◽  
Normal Tissues ◽  
Organ Specific ◽  
Breast Cells ◽  
Normal Human ◽  
Selective Localization ◽  
Host Parasite

Rabbits immunized with human trophoblast cell membranes produced antibodies that were detected, by immunofluorescence, to react with normal human tissues, and, by complement-mediated cytotoxicity, with several transformed human cell lines. Absorption with trophoblast abolished all of these reactions, whereas multiple absorptions with lymphocytes, liver or kidney failed to remove reactivity with either trophoblast or certain transformed cells. To further identify the antigens responsible for these antibodies, rabbits were immunized with a chromatographed fraction of deoxycholate-solubilized membranes prepared from KCl-extracted, ultracentrifuge-prepared trophoblast micro­villi. The resultant IgG antibody reacted specifically with syncytio- trophoblastic membranes in sections of human placentae, in addition to recognizing the membranes of viable Chang liver, AV 3 , HEp-2, Sw/156 (kidney) and Sw/527 (breast) cells. That normal tissues, baboon or monkey placentae, and HeLa or Daudi cell lines did not react with this antibody, indicates the presence of species-and organ-specific antigens in human trophoblast, as well as the existence of trophoblast cross-reactive antigens on some transformed cells. The selective localization of these antigens at the interface of the materno-foetal graft suggests that they function biologically in the host-parasite relation of human pregnancy; their appearance on many transformed cells implies a similar function in the host-parasite relation of some human cancers.

scholarly journals Genome-wide quantification of rare somatic mutations in normal human tissues using massively parallel sequencing

2016 ◽  
Vol 113 (35) ◽  
pp. 9846-9851 ◽  
Author(s):  
Margaret L. Hoang ◽  
Isaac Kinde ◽  
Cristian Tomasetti ◽  
K. Wyatt McMahon ◽  
Thomas A. Rosenquist ◽  
...  
Keyword(s):  
Massively Parallel Sequencing ◽  
Point Mutations ◽  
Genetic Alterations ◽  
Human Tissues ◽  
Molecular Barcoding ◽  
Normal Tissues ◽  
Rare Mutations ◽  
Normal Human ◽  
Nuclear Genomes ◽  
Mutation Spectra

We present the bottleneck sequencing system (BotSeqS), a next-generation sequencing method that simultaneously quantifies rare somatic point mutations across the mitochondrial and nuclear genomes. BotSeqS combines molecular barcoding with a simple dilution step immediately before library amplification. We use BotSeqS to show age- and tissue-dependent accumulations of rare mutations and demonstrate that somatic mutational burden in normal human tissues can vary by several orders of magnitude, depending on biologic and environmental factors. We further show major differences between the mutational patterns of the mitochondrial and nuclear genomes in normal tissues. Lastly, the mutation spectra of normal tissues were different from each other, but similar to those of the cancers that arose in them. This technology can provide insights into the number and nature of genetic alterations in normal tissues and can be used to address a variety of fundamental questions about the genomes of diseased tissues.

scholarly journals A body map of somatic mutagenesis in morphologically normal human tissues

2020 ◽  
Author(s):  
Ruoyan Li ◽  
Lin Di ◽  
Jie Li ◽  
Wenyi Fan ◽  
Yachen Liu ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Genomic Analysis ◽  
Driver Mutations ◽  
Human Tissues ◽  
Normal Tissues ◽  
Variable Extent ◽  
Normal Human ◽  
Body Map ◽  
Somatic Mutagenesis ◽  
Mutational Processes

AbstractSomatic mutations accumulated in normal tissues are associated with aging and disease. Here, we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies (~ 600 cells each), mostly from the epithelia, of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although with variable extent, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for tissues from esophagus and cardia. Endogenous mutational processes like SBS1 and SBS5 are ubiquitous among normal tissues though exhibiting different relative activities. Exogenous mutational processes like SBS22 were found in different tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In epithelial tissues from esophagus and cardia, macroscopic somatic clones expanded to several millimeters were frequently seen, whereas in tissues from colon, rectum, and duodenum somatic clones were microscopic in size and evolved independently. Our study depicted a body map of somatic mutations and clonal expansions from the same individuals, and it revealed that the degree of somatic clonal expansion and enrichment of driver mutations are highly organ specific.

scholarly journals Expression of Transcription Factor CREM in Human Tissues

2021 ◽  
pp. 002215542110320
Author(s):  
Heidi Kaprio ◽  
Vanina D. Heuser ◽  
Katri Orte ◽  
Mikko Tukiainen ◽  
Ilmo Leivo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Cancer Biology ◽  
Target Genes ◽  
Protein Isoforms ◽  
Human Tissues ◽  
Fusion Genes ◽  
Mesenchymal Tumors ◽  
Normal Tissues ◽  
Normal Human

Cyclic AMP element modulator (CREM) is a transcription factor best known for its intricate involvement in spermatogenesis. The CREM gene encodes for multiple protein isoforms, which can enhance or repress transcription of target genes. Recent studies have identified fusion genes, with CREM as a partner gene in many neoplastic diseases. EWSR1-CREM fusion genes have been found in several mesenchymal tumors and in salivary gland carcinoma. These genes encode fusion proteins that include the C-terminal DNA-binding domain of CREM. We used a transcriptomic approach and immunohistochemistry to study the expression of CREM isoforms that include DNA-binding domains across human tissues. We found that CREM protein is widely expressed in almost all normal human tissues. A transcriptomic analysis of normal tissues and cancer showed that transcription of CREM can be altered in tumors, suggesting that also wild-type CREM may be involved in cancer biology. The wide expression of CREM protein in normal human tissues and cancer may limit the utility of immunohistochemistry for identification of tumors with CREM fusions:

Cytoprotective Agents to Avoid Chemotherapy Induced Sideeffects on Normal Cells: A Review

2019 ◽  
Vol 19 (10) ◽  
pp. 765-781
Author(s):  
Seema Rohilla ◽  
Harish Dureja ◽  
Vinay Chawla
Keyword(s):  
Adverse Effects ◽  
Anticancer Agents ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Vital Role ◽  
Normal Cells ◽  
Normal Tissues ◽  
Organ Specific ◽  
Delay In Treatment

Anticancer agents play a vital role in the cure of patients suffering from malignancy. Though, the chemotherapeutic agents are associated with various adverse effects which produce significant toxic symptoms in the patients. But this therapy affects both the malignant and normal cells and leads to constricted therapeutic index of antimalignant drugs which adversely impacts the quality of patients’ life. Due to these adversities, sufficient dose of drug is not delivered to patients leading to delay in treatment or improper treatment. Chemoprotective agents have been developed either to minimize or to mitigate the toxicity allied with chemotherapeutic agents. Without any concession in the therapeutic efficacy of anticancer drugs, they provide organ specific guard to normal tissues.

scholarly journals Exosomal ANGPTL1 attenuates colorectal cancer liver metastasis by regulating Kupffer cell secretion pattern and impeding MMP9 induced vascular leakiness

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Kai Jiang ◽  
Haiyan Chen ◽  
Yimin Fang ◽  
Liubo Chen ◽  
Chenhan Zhong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Kupffer Cell ◽  
Cell Secretion ◽  
Gene Expressions ◽  
Protein Levels ◽  
Normal Tissues ◽  
Mmp9 Expression ◽  
Stat3 Signaling Pathway

Abstract Background Angiopoietin-like protein 1 (ANGPTL1) has been proved to suppress tumor metastasis in several cancers. However, its extracellular effects on the pre-metastatic niches (PMNs) are still unclear. ANGPTL1 has been identified in exosomes, while its function remains unknown. This study was designed to explore the role of exosomal ANGPTL1 on liver metastasis in colorectal cancer (CRC). Methods Exosomes were isolated by ultracentrifugation. The ANGPTL1 level was detected in exosomes derived from human CRC tissues. The effects of exosomal ANGPTL1 on CRC liver metastasis were explored by the intrasplenic injection mouse model. The liver PMN was examined by vascular permeability assays. Exosomal ANGPTL1 localization was validated by exosome labeling. The regulatory mechanisms of exosomal ANGPTL1 on Kupffer cells were determined by RNA sequencing. qRT-PCR, Western Blot, and ELISA analysis were conducted to examine gene expressions at mRNA and protein levels. Results ANGPTL1 protein level was significantly downregulated in the exosomes derived from CRC tumors compared with paired normal tissues. Besides, exosomal ANGPTL1 attenuated liver metastasis and impeded vascular leakiness in the liver PMN. Moreover, exosomal ANGPTL1 was mainly taken up by KCs and regulated the KCs secretion pattern, enormously decreasing the MMP9 expression, which finally prevented the liver vascular leakiness. In mechanism, exosomal ANGPTL1 downregulated MMP9 level in KCs by inhibiting the JAK2-STAT3 signaling pathway. Conclusions Taken together, exosomal ANGPTL1 attenuated CRC liver metastasis and impeded vascular leakiness in the liver PMN by reprogramming the Kupffer cell and decreasing the MMP9 expression. This study suggests a suppression role of exosomal ANGPTL1 on CRC liver metastasis and expands the approach of ANGPTL1 functioning.

scholarly journals IMMUNOLOGIC STUDIES OF WATER-SOLUBLE HUMAN AMYLOID FIBRILS

1969 ◽  
Vol 130 (4) ◽  
pp. 797-808 ◽  
Author(s):  
Edward C. Franklin ◽  
Mordechai Pras
Keyword(s):  
Human Serum ◽  
Comparative Studies ◽  
Amyloid Fibrils ◽  
Complement Fixation ◽  
Cross Reactivity ◽  
Water Soluble ◽  
Antigenic Determinants ◽  
Normal Tissues ◽  
Absorption Studies ◽  
Normal Human

Eight preparations of soluble amyloid and degraded amyloid (DAM) were compared immunologically. Unlike amyloid fibrils, six of eight preparations of DAM proved to be relatively strong immunogens. Antisera to DAM reacted weakly or not at all with normal human serum or extracts of normal tissues, but were specifically reactive with amyloid fibrils or DAM. Comparative studies of DAM'S from eight different subjects showed some degree of cross-reactivity among them, yet demonstrated that they were not identical. Similar conclusions were obtained by quantitative precipitin and complement fixation analyses. Comparison of the amyloid fibrils with the homologous DAM by complement fixation and absorption studies demonstrated the existence in DAM of antigenic determinants that were lacking or inaccessible in the native fibrils. A search for amyloid precursors and antibodies to amyloid in the sera of 12 patients proved unsuccessful.

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