scholarly journals Overview of the Soluble and Membrane-bound Tumor Factors Limiting NKmediated Immune Surveillance

2017 ◽  
Vol 03 (01) ◽  
Author(s):  
Cristina Bottino ◽  
Mariella Della Chiesa ◽  
Alessandra Dondero ◽  
Francesca Bellora ◽  
Beatrice Casu ◽  
...  
Keyword(s):  
Immune Surveillance ◽  
Membrane Bound

scholarly journals Monitoring and characterizing soluble and membrane-bound ectonucleotidases CD73 and CD39

2019 ◽  
Author(s):  
Said A. Goueli ◽  
Kevin Hsiao
Keyword(s):  
Small Molecules ◽  
Adenosine Receptors ◽  
Immune Surveillance ◽  
Effector T Cell ◽  
Cell Functions ◽  
Novel Drugs ◽  
Speed Up ◽  
Membrane Bound ◽  
Effective Cancer Therapy

AbstractThe success of immunotherapy treatment in oncology ushered a new modality for treating a wide variety of cancers. However, lack of effect in some patients made it imperative to identify other pathways that are exploited by cancer cells to circumvent immune surveillance, and possibly synergize immune checkpoint treatment in those cases. It has been recently recognized that adenosine levels increased significantly in the tumor microenvironment and that adenosine/adenosine receptors play a powerful role as immunosuppressant and attenuating several effector T cell functions. The two main enzymes responsible for generating adenosine in the microenvironment are the ectonucleotidases CD39 and CD73, the former utilizes both ATP and ADP and producing AMP while the latter utilizes AMP and generates adenosine. Thus, these two enzymes combined are the major source for the bulk of adenosine produced in the microenvironment. They were shown to be validated targets in oncology leading to several clinical trials that include small molecules as well as antibodies, showing positive and encouraging results in the preclinical arena. Towards the development of novel drugs to target these enzymes, we have developed a platform that can be utilized to monitor the activities of both enzymes in vitro (biochemical) as well as in cells (cell based) assays. We have developed very sensitive and homogenous assays that enabled us to monitor the activity of both enzymes and demonstrate selectivity of known inhibitors as well as monoclonal antibodies. This should speed up screening for novel inhibitors leading to more effective cancer therapy

scholarly journals Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls

2021 ◽  
Vol 8 ◽  
Author(s):  
Alexandra Lushnikova ◽  
Johan Bohr ◽  
Anna Wickbom ◽  
Andreas Münch ◽  
Klas Sjöberg ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Surveillance ◽  
Collagenous Colitis ◽  
Microscopic Colitis ◽  
Protective Effects ◽  
Galectin 3 ◽  
Membrane Bound ◽  
Histological Remission ◽  
Colonic Biopsies ◽  
Active Disease

Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients.Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58).Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls.Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.

scholarly journals Insights Into the Regulation of Gynecological Inflammation-Mediated Malignancy by Metalloproteinases

2021 ◽  
Vol 9 ◽  
Author(s):  
Yasmin Begum ◽  
Anuradha Pandit ◽  
Snehasikta Swarnakar
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Low Income ◽  
Expression Patterns ◽  
Immune Surveillance ◽  
Reproductive Age ◽  
Cellular Interactions ◽  
Gynecological Disorders ◽  
Membrane Bound ◽  
A Disintegrin And Metalloproteinase

Gynecological illness accounts for around 4.5% of the global disease burden, which is higher than other key global health concerns such as malaria (1.04%), TB (1.9%), ischemic heart disease (2.2%), and maternal disorders (3.5%). Gynecological conditions in women of reproductive age are linked to both in terms of diagnosis and treatment, especially in low-income economies, which poses a serious social problem. A greater understanding of health promotion and illness management can help to prevent diseases in gynecology. Due to the lack of established biomarkers, the identification of gynecological diseases, including malignancies, has proven to be challenging in most situations, and histological exams remain the gold standard. Metalloproteinases (MMPs, ADAMs, ADAMTSs) and their endogenous inhibitors (TIMPs) modulate the protease-dependent bioavailability of local niche components (e.g., growth factors), matrix turnover, and cellular interactions to govern specific physical and biochemical characteristics of the environment. Matrix metalloproteinases (MMPs), A Disintegrin and Metalloproteinase (ADAM), and A Disintegrin and Metalloproteinase with Thrombospondin Motif (ADAMTS) are zinc-dependent endopeptidases that contribute significantly to the disintegration of extracellular matrix proteins and shedding of membrane-bound receptor molecules in several diseases, including arthritis. MMPs are noteworthy genes associated with cancer development, functional angiogenesis, invasion, metastasis, and immune surveillance evasion. These genes are often elevated in cancer and multiple benign gynecological disorders like endometriosis, according to research. Migration through the extracellular matrix, which involves proteolytic activity, is an essential step in tumor cell extravasation and metastasis. However, none of the MMPs’ expression patterns, as well as their diagnostic and prognostic potential, have been studied in a pan-cancer context. The latter plays a very important role in cell signaling and might be used as a cancer treatment target. ADAMs are implicated in tumor cell proliferation, angiogenesis, and metastasis. This review will focus on the contribution of the aforementioned metalloproteinases in regulating gynecological disorders and their subsequent manipulation for therapeutic intervention.

Two Distinct Types of Microfilaments in the Cytoplasm of Human Adenohypophysial Cells

1973 ◽  
Vol 31 ◽  
pp. 668-669
Author(s):  
E. Horvath ◽  
K. Kovacs ◽  
I. E. Stratmann ◽  
C. Ezrin
Keyword(s):  
Pituitary Tumors ◽  
Average Diameter ◽  
Anterior Lobe ◽  
Uranyl Acetate ◽  
Type I ◽  
Breast Cancer Patients ◽  
Human Pituitary ◽  
Severe Diabetes ◽  
Pituitary Glands ◽  
Membrane Bound

Surgically removed human pituitary glands as well as pituitary tumors fixed in glutaraldehyde, postfixed in osmium tetroxide, embedded in epon resin, stained with uranyl acetate and lead citrate have been investigated by electron microscopy in order to correlate ultrastructure with functional activity. In the course of this study two distinct types of microfilaments have been identified in the cytoplasm of adenohypophysiocytes.Type I microfilaments (Fig. 1) were found in the cytoplasm of anterior lobe cells of five female subjects with disseminated mammary cancer and two patients with severe diabetes mellitus. The breast cancer patients were treated pre-operatively for various periods of time with different doses of oxysteroids. The microfilaments had an average diameter of JO A, formed parallel bundles, were scattered irregularly in the cytoplasm and were frequently located in the perikaryon. They were not membrane-bound and failed to show any periodicity.

Intranuclear Crystals in Regenerating Canine Kidneys

1973 ◽  
Vol 31 ◽  
pp. 412-413
Author(s):  
D.G. Osborne ◽  
L.J. McCormack ◽  
M.O. Magnusson ◽  
W.S. Kiser
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Tubular Epithelial Cell ◽  
Tubular Epithelial Cells ◽  
Cell Nuclei ◽  
Crystalline Structures ◽  
Small Crystals ◽  
Membrane Bound

During a project in which regenerative changes were studied in autotransplanted canine kidneys, intranuclear crystals were seen in a small number of tubular epithelial cells. These crystalline structures were seen in the control specimens and also in regenerating specimens; the main differences being in size and number of them. The control specimens showed a few tubular epithelial cell nuclei almost completely occupied by large crystals that were not membrane bound. Subsequent follow-up biopsies of the same kidneys contained similar intranuclear crystals but of a much smaller size. Some of these nuclei contained several small crystals. The small crystals occurred at one week following transplantation and were seen even four weeks following transplantation. As time passed, the small crystals appeared to fuse to form larger crystals.

Membrane-bound vesicles associated with the microvilli in the midgut of the freshwater microcrustacean, Daphnia magna

1983 ◽  
Vol 41 ◽  
pp. 480-481
Author(s):  
Patricia L. Jansma
Keyword(s):  
Daphnia Magna ◽  
Intestinal Epithelial Cells ◽  
Uranyl Acetate ◽  
Intestinal Epithelial ◽  
Chlamydomonas Reinhardii ◽  
Thin Sections ◽  
Saturated Water ◽  
Cacodylate Buffer ◽  
Membrane Bound ◽  
Ethanol Series

The presence of the membrane bound vesicles or blebs on the intestinal epithelial cells has been demonstrated in a variety of vertebrates such as chicks, piglets, hamsters, and humans. The only invertebrates shown to have these microvillar blebs are two species of f1ies. While investigating the digestive processes of the freshwater microcrustacean, Daphnia magna, the presence of these microvillar blebs was noticed.Daphnia magna fed in a suspension of axenically grown green alga, Chlamydomonas reinhardii for one hour were narcotized with CO2 saturated water. The intestinal tracts were excised in 2% glutaraldehyde in 0.2 M cacodyl ate buffer and then placed in fresh 2% glutaraldehyde for one hour. After rinsing in 0.1 M cacodylate buffer, the sample was postfixed in 2% OsO4, dehydrated with a graded ethanol series, infiltrated and embedded with Epon-Araldite. Thin sections were stained with uranyl acetate and Reynolds lead citrate before viewing with the Philips EM 200.

Analysis of the Anterior Secretory Cells of Onchidohs Muricata (Nudibranchia)

1981 ◽  
Vol 39 ◽  
pp. 614-615
Author(s):  
Roy Skidmore
Keyword(s):  
Endoplasmic Reticulum ◽  
Secretory Granules ◽  
Golgi Body ◽  
The Body ◽  
Secretory Cells ◽  
Secretory Vesicles ◽  
High Magnification ◽  
Large Numbers ◽  
Membrane Bound ◽  
Sole Of The Foot

The long-necked secretory cells in Onchidoris muricata are distributed in the anterior sole of the foot. These cells are interspersed among ciliated columnar and conical cells as well as short-necked secretory gland cells. The long-necked cells contribute a significant amount of mucoid materials to the slime on which the nudibranch travels. The body of these cells is found in the subepidermal tissues. A long process extends across the basal lamina and in between cells of the epidermis to the surface of the foot. The secretory granules travel along the process and their contents are expelled by exocytosis at the foot surface.The contents of the cell body include the nucleus, some endoplasmic reticulum, and an extensive Golgi body with large numbers of secretory vesicles (Fig. 1). The secretory vesicles are membrane bound and contain a fibrillar matrix. At high magnification the similarity of the contents in the Golgi saccules and the secretory vesicles becomes apparent (Fig. 2).

An Electron Microscopic Study of the Acute Effects of Hypothalamic Releasing Factors on the Anterior Pituitary Gland

1968 ◽  
Vol 26 ◽  
pp. 232-233
Author(s):  
P.W. Coates ◽  
E.A. Ashby ◽  
L. Krulich ◽  
A. Dhariwal ◽  
S. McCann
Keyword(s):  
Anterior Pituitary ◽  
Microscopic Investigation ◽  
Uranyl Acetate ◽  
Electron Microscopic Investigation ◽  
Electron Microscopic ◽  
Tissue Samples ◽  
Thin Sections ◽  
Dense Membrane ◽  
Membrane Bound ◽  
Releasing Factors

The morphologic effects on somatotrophs of crude sheep hypothalamic extract prepared from stalk-median eminence were studied by electron microscopy in conjunction with concurrently run bioassays performed on the same tissue samples taken from young adult male Sherman rats.Groups were divided into uninjected controls and injected experimentals sacrificed at 5', 15', and 30' after injection. Half of each anterior pituitary was prepared for electron microscopic investigation, the other half for bioassay. Fixation using collidine buffered osmium tetroxide was followed by dehydration and embedment in Maraglas. Uranyl acetate and lead citrate were used as stains. Thin sections were examined in a Philips EM 200.Somatotrophs from uninjected controls appeared as described in the literature (Fig. 1). In addition to other components, these cells contained moderate numbers of spherical, electron-dense, membrane-bound granules approximately 350 millicrons in diameter.

A High Resolution Cytochemical Study of Nuclear ATPase in Human Spermatozoa

1975 ◽  
Vol 33 ◽  
pp. 594-595
Author(s):  
A. Sosa ◽  
L. Calzada
Keyword(s):  
High Resolution ◽  
Atpase Activity ◽  
Nuclear Membrane ◽  
Human Sperm ◽  
Sperm Nucleus ◽  
Human Spermatozoa ◽  
Cytochemical Study ◽  
Membrane Bound ◽  
Sperm Nuclei ◽  
Interchromatin Space

The dependence of nuclear metabolism on the function of the nuclear membrane is not well understood. Whether or not the function of the nuclear membrane is partial or totally responsible of the repressed template activity of human sperm nucleus has not at present been elucidated. One of the membrane-bound enzymatic activities which is concerned with the mechanisms whereby substances are thought to cross cell membranes is adenosintriphosphatase (ATPase). This prompted its characterization and distribution by high resolution photogrammetry on isolated human sperm nuclei. Isolated human spermatozoa nuclei were obtained as previously described. ATPase activity was demonstrated by the method of Wachstein and Meisel modified by Marchesi and Palade. ATPase activity was identified as dense and irregularly distributed granules confined to the internal leaflet of the nuclear membrane. Within the nucleus the appearance of the reaction product occurs as homogenous and dense precipitates in the interchromatin space.

Spindle shaped bodies in foveolar cones of the baboon retina

1989 ◽  
Vol 47 ◽  
pp. 960-961
Author(s):  
W. Krebs ◽  
I. Krebs
Keyword(s):  
Cross Sections ◽  
Inclusion Bodies ◽  
Photoreceptor Cells ◽  
Papio Anubis ◽  
Retinal Photoreceptor ◽  
Age Related ◽  
Cone Cells ◽  
Membrane Bound ◽  
Oriented Parallel ◽  
Shaped Inclusion

Various inclusion bodies occur in vertebrate retinal photoreceptor cells. Most of them are membrane bound and associated with phagocytosis or they are age related residual bodies. We found an additional inclusion body in foveal cone cells of the baboon (Papio anubis) retina.The eyes of a 15 year old baboon were fixed by immersion in cacodylate buffered glutaraldehyde (2%)/formaldehyde (2%) as described in detail elsewhere . Pieces of retina from various locations, including the fovea, were embedded in epoxy resin such that radial or tangential sections could be cut.Spindle shaped inclusion bodies were found in the cytoplasm of only foveal cones. They were abundant in the inner segments, close to the external limiting membrane (Fig. 1). But they also occurred in the outer fibers, the perikarya, and the inner fibers (Henle’s fibers) of the cone cells. The bodies were between 0.5 and 2 μm long. Their central diameter was 0.2 to 0. 3 μm. They always were oriented parallel to the long axis of the cone cells. In longitudinal sections (Figs. 2,3) they seemed to have a fibrous skeleton that, in cross sections, turned out to consist of plate-like (Fig.4) and tubular profiles (Fig. 5).

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