Leukemia Thymus

Lymphocytic Tumors of Thymic Origin. The appearance of spontaneous tumors (e. . SAKRTLS-13) in AKR and C58 mice (27) is quite common. Other thymic tumors can also be induced chemically (28) (BALENTL—3, -5 or P-1798 Table I) or virally (Moloney leukemia virus (29)). in the early stage of tumor development they are confined to the thymus, but later the tumor is metastasized to the spleen, liver, kidney, and lymph nodes. 

Experimental data in animals and studies of human cases of benzene intoxication indicate a link between the decrease in bone marrow cellularity and the development of leukemia. Many cases of benzene-induced leukemia appear to have been preceded by aplastic anemia (Toft et al. 1982). The compensatory response (regenerative hyperplasia) observed in the bone marrow, thymus, and spleen of exposed animals may play a role in the carcinogenic response (Rozen and Snyder 1985 Snyder 1987 Snyder and Koscis 1975 Snyder etal. 1984). 

Y Ichinohe T, Tsunetsugu-Yokota Y, Katano H, Takahashi H, Matsuda J, Sata T, Kurata T, Nagashima K, HaU WW (2006) Thymus-derived leukemia-lymphoma in mice transgenic for the Tax gene of human T-lymphotropic virus type I. Nat Med 12 466 72. 

There is limited evidence of carcinogenicity of azathioprine in experimental animals. Studies with rats produced squamous cell carcinomas of the ear duct after administration at 150 mg kg in the diet for 52 weeks and lymphomas of the thymus gland under other conditions. In mice, intraperitoneal injections at 40 mg kg in 1-4-day-old offspring produced leukemia and long-term studies produced lymphoma and hemangiodothelioma of the uterus. 

B- and T-cell neoplasms are divided into precursor disorders (lymphoblastic leukemias and lymphomas) with normal counterparts in the earliest bone marrow and thymus compartments, and mature, or peripheral, malignancies akin to normal extrathymic, nodal, splenic, or circulating lymphocytes. Discussion is focused on those malignancies commonly diagnosed using immunohistochemistry (i.e., solid tumors). 

There are a number of other diseases that have been associated with aberrations of serum thymic hormone bioactivity, and these are listed in Table 1. It is noteworthy that serum thymic hormone bioactivity has been found to be low in 25% to 50% of patients with systemic lupus erythematosus (Bach et al., 1975 Twomey et al., 1979 Iwata et al., 1981 Lewis et al., 1981), Hodgkin s disease (Schulof et al., 1981), and acute lymphoblastic leukemia (Twomey et al., 1980). In all of these studies it has not been possible to correlate abnormalities of serum thymic hormone bioactivity with specific defects of T cell immunity. Thus, it remains to be established whether low serum thymic hormone levels in autoimmune or neoplastic disorders reflect an etiologic role for thymus dysfunction in these disease processes or merely a secondary manifestation of the diseases themselves. In patients with acute lymphoblastic leukemia it was demonstrated that the low bioactivity detected in the Twomey assay was related to a circulating inhibitor of thymopoietinlike bioactivity (Twomey et al., 1980). Thus, it is possible that other secondary immunodeficiencies that are associated with depressed serum thymic-hormonelike bioactivity may also reflect the presence of circulating inhibitors to thymic hormones rather than an absolute deficiency in their production. 

Moderately irritating upon direct contact severe burns may result. Vapors highly irritating to eyes and respiratory tract. Testicular atrophy, leukemia, and necrosis of the thymus In test animals. Topical application causes skin cancer in animal studies. 

A pyrimidine phosphoribosyltransferase activity with a broader specificity than the yeast enzyme has been demonstrated in animal tissues. Highly purified preparations from calf thymus (15) and beef erythrocytes (16) accepted orotate and 5-fluorouracil as substrates. Uracil phosphoribosyltransferase activity has also been demonstrated in extracts from mouse leukemia cells. Fluorouracil is a better substrate for this enzyme than uracil at pH 7.5, possibly because the acid dissociation constant for the analogue (pif 8.15) is higher than that of uracil (pK, 9.45) (17). This reasoning would suggest that the anionic form of the substrate might be the species required by the enzyme. This enzyme has been implicated in the... 

The alkaloid (H-)-thalicarpine has shown cytotoxic activity against human KB cells in monolayer culture, and antitumor activity against the rat Walker 256 carcinosarcoma over a wide dosage range.Cardiovascular effects such as hypotension and bradycardia were noted in monkeys treated with doses of 2.5 mg/kg and it was proposed that such effects were due to direct myocardial depression in combination with nonspecific vasodilation. Thalicarpine was found to inhibit DNA, RNA, and protein synthesis in mouse L1210 leukemia cells, ° and in a study with tritiated thalicarpine, reversible binding with calf thymus DNA was detected. Thalicarpine was reported to bind to some unidentified human serum component in vivo, and to inhibit aniline hydroxylase activity of rat liver microsomes. Thalicarpine was submitted to clinical trials, but was soon found to possess serious CNS and/or cardiovascular toxicity at doses below those required for antitumor activity. ... 

Ha (thymus leukemia antigen) F4/80 (macrophage marker) 2.4G2 (Fc receptor)... 

Fig.5). Thus far, the highly pepstatin-sensitive forms of cathepsin D have been found only in the lymphoid tissues of rodents rat spleen, thymus, lymph node cells, and lymphocytes, mouse spleen and thymus, a mouse-derived leukemia L1210 line, and hamster spleen.

The usual source of TDTase is the calf thymus gland. It contains 5-10 mg of TDTase per kg of fresh tissue. The enzyme is also found at high levels (100—200 U/10 cells) in certain leukemic lymphocytes (e.g., human leukemia Molt-4 and mouse thymoma PI 798) and at a detectable level in bone marrow. TDTase activity is not found in prokaryotes nor in unicellular eukaryotes. 

Globehson, A., and Auerbach, R. (1965). In vitro studies on thymus and lung differentiation following urethan treatment. Wistar Inst. Monograph No. 4 (Methodological Approaches to Study of Leukemia), pp. 3-19. 

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