scholarly journals A NATURAL ANTIBODY THAT REACTS IN VITRO WITH A SEDIMENTABLE CONSTITUENT OF NORMAL TISSUE CELLS

1942 ◽  
Vol 76 (6) ◽  
pp. 557-578 ◽  
Author(s):  
John G. Kidd ◽  
William F. Friedewald
Keyword(s):  
Normal Tissue ◽  
High Speed ◽  
Natural Antibody ◽  
Neoplastic Tissue ◽  
Normal Tissues ◽  
Supernatant Liquid ◽  
Tissue Antibody ◽  
Tissue Cells ◽  
Natural Tissue

Continued serological investigations of the sedimentable constituents of normal and neoplastic tissues have shown that the blood serum of normal rabbits will fix complement in mixture with saline extracts of normal rabbit tissues. The phenomenon has proved referable, not to anticomplementary effects of serum or antigen nor to so called non-specific complement fixation, but to a naturally occurring serum principle, hitherto unrecognized, which reacts specifically in vitro with a sedimentable constituent of normal tissue cells. The principle exists in the blood of nearly all adult rabbits but is absent from that of rabbits less than 1 month old. It can be salted out from serum with ammonium sulfate and is destroyed when heated at 65°C. for 20 to 30 minutes. Its titer was found to run parallel in general with that of two natural antibodies also present in normal rabbit's blood (natural Wassermann reagin, natural anti-sheep hemolysin); but absorption tests showed it to be distinct from these. Because of its properties, the serum principle has been termed the natural tissue antibody. The substance with which the natural tissue antibody reacts is regularly present in saline extracts of many normal tissues,—those of rabbits and of other species as well. Kidney and liver tissues always yield it in abundance, while spleen, brain, and testicle provide somewhat less; heart and voluntary muscle extracts contain relatively little, and non-nucleated erythrocytes and skin are practically devoid of it. The results of affinity and absorption tests indicate that it is nearly or quite the same from whatever tissue or species derived. It is readily sedimentable in the high-speed centrifuge, little or none remaining in the supernatant liquid of potent suspensions spun at 25,000 R.P.M. (45,400 g) for 1 hour. It either does not come away into alcohol or is inactivated thereby, is readily destroyed by heat (56–70°C. for 30 minutes), and diminishes notably in antigenic potency upon standing overnight in saline suspension or when the tissues containing it are kept in glycerol. Its properties suggest that it may be a protein. The implications of the findings are discussed in relation to the formation of the natural antibody and its place amongst serological phenomena, to so called "non-specific" fixation of complement and other serological complexities, and with particular reference to the character of the sedimentable constituents of normal and neoplastic tissue cells.

scholarly journals A NATURAL ANTIBODY THAT REACTS IN VITRO WITH A SEDIMENTABLE CONSTITUENT OF NORMAL TISSUE CELLS

1942 ◽  
Vol 76 (6) ◽  
pp. 543-556 ◽  
Author(s):  
John G. Kidd ◽  
William F. Friedewald
Keyword(s):  
Blood Serum ◽  
Normal Tissue ◽  
Complement Fixation ◽  
Natural Antibody ◽  
Normal Adult ◽  
Controlled Conditions ◽  
Tissue Cells ◽  
Rabbit Tissues

The foregoing experiments have shown that complement fixation takes place when the blood serum of normal adult rabbits is mixed with fresh saline extracts of normal rabbit tissues under controlled conditions. A natural antibody, which reacts in vitro with a sedimentable constituent of normal tissue cells, is responsible for the phenomenon.

scholarly journals INDUCED ANTIBODIES THAT REACT IN VITRO WITH SEDIMENTABLE CONSTITUENTS OF NORMAL AND NEOPLASTIC TISSUE CELLS

1945 ◽  
Vol 82 (1) ◽  
pp. 21-39 ◽  
Author(s):  
William F. Friedewald ◽  
John G. Kidd
Keyword(s):  
High Speed ◽  
Natural Antibodies ◽  
Carcinoma Cells ◽  
Neoplastic Tissue ◽  
Serological Studies ◽  
New Hosts ◽  
Embryo Tissue ◽  
Tissue Cells ◽  
Rabbit Tissues

Antibodies were found in the blood of certain rabbits carrying one or another of four transplanted cancers (Brown-Pearce and V2 carcinomas; RSI and Kato sarcomas) which will fix complement in vitro in mixture with saline extracts of various normal and neoplastic rabbit tissues—including liver, kidney, spleen, and the four tumors mentioned—and chick embryo tissue as well. These antibodies, which have been called induced tissue antibodies, are similar to the natural antibodies previously described (2) in that they react with those constituents of the various tissue cells that prove readily sedimentable in the high speed centrifuge; they differ from the natural antibodies in being absent from the blood of normal rabbits and in withstanding 65° C. for 30 minutes. Certain quantitative differences suggest that the induced tissue antibodies have somewhat various affinities, depending in part upon the type of neoplasm carried by the host. They may perhaps be consequent on antigenic differences between the sedimentable constituents of the tumor cells and those of the new hosts; for they were not found in the blood of rabbits carrying papillomas and cancers composed of the animals' own cells, and not in that of rabbits in which multiple vaccinia or fibroma virus lesions had recently regressed. The characters of the sedimentable constituents of normal and neoplastic tissue cells, as revealed thus far by chemical, morphological, and serological studies, have recently been discussed (2,8). In this relation, it has seemed essential to recognize the induced antibodies here described, particularly since they may complicate serological studies aimed at disclosing distinctive sedimentable substances in tissue cells. In an associated paper experiments are reported which bear upon the relation between the induced tissue antibodies and an antibody that reacts specifically with a distinctive sedimentable constituent of Brown-Pearce carcinoma cells (7).

SOME BIOLOGICAL PROBLEMS IN CANCER BIOCHEMISTRY

1960 ◽  
Vol 38 (4) ◽  
pp. 425-433 ◽  
Author(s):  
Louis Siminovitch ◽  
Arthur Axelrad
Keyword(s):  
Normal Tissue ◽  
Normal Growth ◽  
Cell Types ◽  
Biological Properties ◽  
Cellular Level ◽  
Animal Cells ◽  
Biochemical Basis ◽  
Normal Tissues ◽  
Ascites Tumors

Understanding of the cancer process in chemical terms has been seriously hampered by the difficulty of interpreting results of biochemical comparisons between masses of tumor and of normal tissue. Normal tissue consists of a variety of cell types and tumors may originate from one or more of these. As whole masses, therefore, normal tissues cannot serve as adequate controls for experiments on any single tumor. Tumor cell populations, even those arising from a single cell type, are themselves cytogenetically and continually undergoing changes during growth (progression). It is thus difficult, if not impossible, to separate the relevant from the irrelevant biochemical features of malignancy.Progress in this field requires means of dealing with the problem of biological heterogeneity. Several biochemical approaches that are free from the hazards of heterogeneity and which have already yielded valuable results, or appear promising, are indicated. These include: (1) The use of ascites tumors for studying the biochemical machinery of cells. No normal tissue exists, however, that could serve as satisfactory control. (2) Biochemical comparisons between pairs of tumor lines which differ by only one inherited characteristic of malignancy. These might reveal a biochemical basis for the biological properties of tumor cells with different degrees of malignancy. (3) Elucidation of normal growth-controlling mechanisms between cells, e.g. action of hormones at the cellular level, and within cells, e.g. mechanism of feed-back control of enzymes and metabolic pathways. (4) Further research into the biochemistry of plant tumor induction in vitro. Here biochemical changes associated with inherited changes leading to nutritional autonomy and uncontrolled growth have already been demonstrated. (5) Studies on the biochemical events during induction of malignancy by viruses in clonal cultures of animal cells in vitro. These could serve as useful models of the whole process of carcinogenesis.

SOME BIOLOGICAL PROBLEMS IN CANCER BIOCHEMISTRY

1960 ◽  
Vol 38 (1) ◽  
pp. 425-433
Author(s):  
Louis Siminovitch ◽  
Arthur Axelrad
Keyword(s):  
Normal Tissue ◽  
Normal Growth ◽  
Cell Types ◽  
Biological Properties ◽  
Cellular Level ◽  
Animal Cells ◽  
Biochemical Basis ◽  
Normal Tissues ◽  
Ascites Tumors

Understanding of the cancer process in chemical terms has been seriously hampered by the difficulty of interpreting results of biochemical comparisons between masses of tumor and of normal tissue. Normal tissue consists of a variety of cell types and tumors may originate from one or more of these. As whole masses, therefore, normal tissues cannot serve as adequate controls for experiments on any single tumor. Tumor cell populations, even those arising from a single cell type, are themselves cytogenetically and continually undergoing changes during growth (progression). It is thus difficult, if not impossible, to separate the relevant from the irrelevant biochemical features of malignancy.Progress in this field requires means of dealing with the problem of biological heterogeneity. Several biochemical approaches that are free from the hazards of heterogeneity and which have already yielded valuable results, or appear promising, are indicated. These include: (1) The use of ascites tumors for studying the biochemical machinery of cells. No normal tissue exists, however, that could serve as satisfactory control. (2) Biochemical comparisons between pairs of tumor lines which differ by only one inherited characteristic of malignancy. These might reveal a biochemical basis for the biological properties of tumor cells with different degrees of malignancy. (3) Elucidation of normal growth-controlling mechanisms between cells, e.g. action of hormones at the cellular level, and within cells, e.g. mechanism of feed-back control of enzymes and metabolic pathways. (4) Further research into the biochemistry of plant tumor induction in vitro. Here biochemical changes associated with inherited changes leading to nutritional autonomy and uncontrolled growth have already been demonstrated. (5) Studies on the biochemical events during induction of malignancy by viruses in clonal cultures of animal cells in vitro. These could serve as useful models of the whole process of carcinogenesis.

scholarly journals c-Jun-like Immunoreactivity in Apoptosis Is the Result of a Crossreaction with Neoantigenic Sites Exposed by Caspase-3-mediated Proteolysis

2002 ◽  
Vol 50 (7) ◽  
pp. 961-972 ◽  
Author(s):  
Joan Ribera ◽  
Victoria Ayala ◽  
Josep E. Esquerda
Keyword(s):  
Normal Tissue ◽  
Caspase 3 ◽  
Tunel Staining ◽  
Apoptotic Cells ◽  
Tissue Samples ◽  
Normal Tissues ◽  
Tissue Sections ◽  
Dying Cells ◽  
Active Caspase

Previous reports in various cells and species have shown that apoptotic cells are specifically and strongly labeled by certain c-Jun/N-terminal antibodies, such as c-Jun/sc45. This kind of immunoreactivity is confined to the cytoplasm. It is not due to c-Jun but appears to be related to c-Jun-like neoepitopes generated during apoptosis. This study was planned to gain further information about c-Jun-like immunostaining during apoptosis and to evaluate these antibodies as possible tools for characterizing cell death. Most of the experiments were performed in chick embryo spinal cord. When the apoptotic c-Jun-like immunoreactivity and caspase-3 immunostaining patterns were compared, we found that both antibodies immunostained the same dying cells in a similar pattern. In contrast to TUNEL staining, which reveals a positive reaction in both apoptotic and necrotic dying cells, active caspase-3 and c-Jun/sc45 antibodies are more selective because they stained only apoptotic cells. When cytosolic extracts from normal tissues were digested in vitro with caspase-3, c-Jun/sc45 immunoreactivity was strongly induced in several proteins, as demonstrated by Western blotting. Similar results were found when normal tissue sections were treated with caspase-3. Our results show that c-Jun/sc45 antibodies react with neoepitopes generated from cell proteins cleaved by activated caspases during apoptosis. We conclude that c-Jun/sc45 antibodies may be useful for detecting apoptosis. They can even be used in archival paraffin-embedded tissue samples.

In vitro biological response of cancer and normal tissue cells to proton irradiation not affected by an added magnetic field

2019 ◽  
Vol 137 ◽  
pp. 125-129 ◽  
Author(s):  
Peter W. Nagle ◽  
Marc-Jan van Goethem ◽  
Marco Kempers ◽  
Harry Kiewit ◽  
Antje Knopf ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Normal Tissue ◽  
Proton Irradiation ◽  
Biological Response ◽  
Tissue Cells

Strahlenwirkung am Normalgewebe

2010 ◽  
Vol 49 (S 01) ◽  
pp. S53-S58 ◽  
Author(s):  
W. Dörr
Keyword(s):  
Radiation Exposure ◽  
Normal Tissue ◽  
Radiation Effects ◽  
A Priori ◽  
Cell Loss ◽  
Turnover Time ◽  
Complete Healing ◽  
Internal Radiotherapy ◽  
Normal Tissues ◽  
Chronic Radiation

SummaryThe curative effectivity of external or internal radiotherapy necessitates exposure of normal tissues with significant radiation doses, and hence must be associated with an accepted rate of side effects. These complications can not a priori be considered as an indication of a too aggressive therapy. Based on the time of first diagnosis, early (acute) and late (chronic) radiation sequelae in normal tissues can be distinguished. Early reactions per definition occur within 90 days after onset of the radiation exposure. They are based on impairment of cell production in turnover tissues, which in face of ongoing cell loss results in hypoplasia and eventually a complete loss of functional cells. The latent time is largely independent of dose and is defined by tissue biology (turnover time). Usually, complete healing of early reactions is observed. Late radiation effects can occur after symptom-free latent times of months to many years, with an inverse dependence of latency on dose. Late normal tissue changes are progressive and usually irreversible. They are based on a complex interaction of damage to various cell populations (organ parenchyma, connective tissue, capillaries), with a contribution from macrophages. Late effects are sensitive for a reduction in dose rate (recovery effects).A number of biologically based strategies for protection of normal tissues or for amelioration of radiation effects was and still is tested in experimental systems, yet, only a small fraction of these approaches has so far been introduced into clinical studies. One advantage of most of the methods is that they may be effective even if the treatment starts way after the end of radiation exposure. For a clinical exploitation, hence, the availability of early indicators for the progression of subclinical damage in the individual patient would be desirable. Moreover, there is need to further investigate the molecular pathogenesis of normal tissue effects in more detail, in order to optimise biology based preventive strategies, as well as to identify the precise mechanisms of already tested approaches (e. g. stem cells).

Resveratrol as an Adjuvant for Normal Tissues Protection and Tumor Sensitization

2020 ◽  
Vol 20 (2) ◽  
pp. 130-145 ◽  
Author(s):  
Keywan Mortezaee ◽  
Masoud Najafi ◽  
Bagher Farhood ◽  
Amirhossein Ahmadi ◽  
Dheyauldeen Shabeeb ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Clinical Studies ◽  
Normal Tissue ◽  
Medical Science ◽  
Treatment Modalities ◽  
Radiation Toxicity ◽  
Normal Tissues ◽  
Normal Tissue Toxicity

Cancer is one of the most complicated diseases in present-day medical science. Yearly, several studies suggest various strategies for preventing carcinogenesis. Furthermore, experiments for the treatment of cancer with low side effects are ongoing. Chemotherapy, targeted therapy, radiotherapy and immunotherapy are the most common non-invasive strategies for cancer treatment. One of the most challenging issues encountered with these modalities is low effectiveness, as well as normal tissue toxicity for chemo-radiation therapy. The use of some agents as adjuvants has been suggested to improve tumor responses and also alleviate normal tissue toxicity. Resveratrol, a natural flavonoid, has attracted a lot of attention for the management of both tumor and normal tissue responses to various modalities of cancer therapy. As an antioxidant and anti-inflammatory agent, in vitro and in vivo studies show that it is able to mitigate chemo-radiation toxicity in normal tissues. However, clinical studies to confirm the usage of resveratrol as a chemo-radioprotector are lacking. In addition, it can sensitize various types of cancer cells to both chemotherapy drugs and radiation. In recent years, some clinical studies suggested that resveratrol may have an effect on inducing cancer cell killing. Yet, clinical translation of resveratrol has not yielded desirable results for the combination of resveratrol with radiotherapy, targeted therapy or immunotherapy. In this paper, we review the potential role of resveratrol for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities.

scholarly journals Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001364
Author(s):  
Yan Zhang ◽  
Hui Yang ◽  
Jun Zhao ◽  
Ping Wan ◽  
Ye Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Metabolism ◽  
Vital Role ◽  
Methionine Metabolism ◽  
Promoter Regions ◽  
Normal Tissues ◽  
Methionine Cycle

BackgroundThe activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored.MethodsMonocytes/macrophages were isolated from peripheral blood, tumor tissues or normal tissues from healthy donors or patients with GC. The role of methionine metabolism in the activation of TAMs was evaluated with both in vivo analyses and in vitro experiments. Pharmacological inhibition of the methionine cycle and modulation of key metabolic genes was employed, where molecular and biological analyses were performed.ResultsTAMs have increased methionine cycle activity that are mainly attributed to elevated methionine adenosyltransferase II alpha (MAT2A) levels. MAT2A modulates the activation and maintenance of the phenotype of TAMs and mediates the upregulation of RIP1 by increasing the histone H3K4 methylation (H3K4me3) at its promoter regions.ConclusionsOur data cast light on a novel mechanism by which methionine metabolism regulates the anti-inflammatory functions of monocytes in GC. MAT2A might be a potential therapeutic target for cancer cells as well as TAMs in GC.

scholarly journals The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 855
Author(s):  
Paola Serrano Martinez ◽  
Lorena Giuranno ◽  
Marc Vooijs ◽  
Robert P. Coppes
Keyword(s):  
Signaling Pathways ◽  
Progenitor Cells ◽  
Tissue Regeneration ◽  
Normal Tissue ◽  
Cellular Response ◽  
Adult Tissue ◽  
Tissue Specific ◽  
Radiation Induced

Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.

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