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

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).

1942 ◽  
Vol 76 (6) ◽  
pp. 557-578 ◽  
Author(s):  
John G. Kidd ◽  
William F. Friedewald

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.


1942 ◽  
Vol 76 (6) ◽  
pp. 543-556 ◽  
Author(s):  
John G. Kidd ◽  
William F. Friedewald

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.


Planta Medica ◽  
2014 ◽  
Vol 80 (16) ◽  
Author(s):  
R Paduch ◽  
M Tomczyk ◽  
A Wiater ◽  
A Dudek ◽  
M Pleszczynska ◽  
...  

2020 ◽  
Vol 20 (8) ◽  
pp. 624-637 ◽  
Author(s):  
Qiong Wu ◽  
Manlin Xiang ◽  
Kun Wang ◽  
Zhen Chen ◽  
Lu Long ◽  
...  

Background: Increasing evidence has shown that p62 plays an important role in tumorigenesis. However, relatively little is known about the association between p62 and tumor invasion and metastasis; in addition, its role in NPC (nasopharyngeal carcinoma, NPC) has been rarely investigated. Objective: To investigate the effect of p62 on tumorigenesis and metastasis in nasopharyngeal carcinoma. Methods: Western blotting, immunofluorescent staining and immunohistochemistry were used to evaluate p62 protein expression. Subsequently, cell viability, colony formation, migration, invasion and autophagy assays were performed. anti-p62 autoantibodies in sera were detected by ELISA. These data were correlated with clinicopathological parameters. Results: We confirmed that p62 was significantly up-regulated in NPC tissues. Furthermore, high expression of p62 was observed in NPC cell lines, and especially in the highly metastatic 5-8F cells. In vitro, down-regulation of p62 inhibited proliferation, clone forming ability, autophagy, migration, and invasion in 5-8F cells, whereas p62 overexpression resulted in the opposite effects in 6-10B cells. Moreover, we confirmed that p62 promotes NPC cell proliferation, migration, and invasion by activating ERK (extracellular signal-regulated kinase, ERK). Clinical analysis indicated that high p62 expression correlates with lymph node and distant metastasis (P<0.05). Serum anti-p62 autoantibodies were increased in NPC patients and levels were associated with metastasis. Conclusion : Our data establish p62 targeting ERK as potential determinant in the NPC, which supplies a new pathway to treat NPC. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis and metastasis in NPC.


2021 ◽  
Vol 60 (6) ◽  
pp. 3939-3951
Author(s):  
Francisco Reigosa-Chamorro ◽  
Luís R. Raposo ◽  
Paula Munín-Cruz ◽  
M. Teresa Pereira ◽  
Catarina Roma-Rodrigues ◽  
...  

2021 ◽  
Vol 14 (1) ◽  
pp. 38
Author(s):  
Hyo Jeong Lee ◽  
Pyeonghwa Jeong ◽  
Yeongyu Moon ◽  
Jungil Choi ◽  
Jeong Doo Heo ◽  
...  

Rearranged during transfection (RET), a receptor tyrosine kinase, is activated by glial cell line-derived neurotrophic factor family ligands. Chromosomal rearrangement or point mutations in RET are observed in patients with papillary thyroid and medullary thyroid carcinomas. Oncogenic alteration of RET results in constitutive activation of RET activity. Therefore, inhibiting RET activity has become a target in thyroid cancer therapy. Here, the anti-tumor activity of a novel RET inhibitor was characterized in medullary thyroid carcinoma cells. The indirubin derivative LDD-2633 was tested for RET kinase inhibitory activity. In vitro, LDD-2633 showed potent inhibition of RET kinase activity, with an IC50 of 4.42 nM. The growth of TT thyroid carcinoma cells harboring an RET mutation was suppressed by LDD-2633 treatment via the proliferation suppression and the induction of apoptosis. The effects of LDD-2633 on the RET signaling pathway were examined; LDD-2633 inhibited the phosphorylation of the RET protein and the downstream molecules Shc and ERK1/2. Oral administration of 20 or 40 mg/kg of LDD-2633 induced dose-dependent suppression of TT cell xenograft tumor growth. The in vivo and in vitro experimental results supported the potential use of LDD-2633 as an anticancer drug for thyroid cancers.


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