Follicular cell neoplasms

Osborne-Mendel rats were fed technical-grade heptachlor (73%) males received TWA doses of 1.94 and 3.9 mg/kg/day and females received TWA doses of 1.28 and 2.56 mg/kg/day for 80 weeks (NCI 1977). The results of this study showed a statistically significant increase in follicular cell neoplasms in the thyroid (adenomas and carcinomas) in females fed the high dose compared to controls. This finding was discounted by the investigators, however, because the incidence rates were low and are known to be variable in the control rat population. Rates of tumor incidences in males were not increased. 

At dosages above 30mg/kg in the diet, chlordane interfered with reproduction in rats and mice, but this effect was reversible after exposure ceased." Pre- and postnatal exposures to chlordane altered the development of the immune system in rodents. A dose-related increase in the incidence of hepatocellular carcinomas was found in male and female mice fed approximately 60mg/k chlordane for 80 weeks. In rats, increases in the incidences of thyroid follicular cell neoplasms were observed. ... 

A recent study confirmed that ethylene thiourea was carcinogenic in male and female rats as shown by increased incidences of thyroid follicular cell neoplasms after treatment of up to 250 ppm in the diet for 2 years. In mice, concentrations ranging from 100 to 1000 ppm for 2 years caused liver and pituitary tumors in addition to thyroid tumors. Perinatal exposure up to 8 weeks followed by a control diet for 2 years was not carcinogenic in rats or mice. Combined perinatal-adult ETU exposures produced the same carcinogenic effects as adult-only exposures. 

Chronic oral exposure of rats and mice to MDA and its dihydrochloride is carcinogenic. Treatment-related increases in the incidences of thyroid follicular cell adenomas and hepatocellular neoplasms were observed in mice after chronic ingestion of MDA in drinking water. In rats, increases in the incidences of thyroid follicular cell carcinoma and hepatic nodules were observed in males and thyroid follicular cell ademonas occurred in females. Although not statistically significant, certain uncommon tumors such as bile duct adenomas, papillomas of the urinary bladder, and granulosa cell tumors of the ovary also were reported. These tumors are of low incidence in historical controls. In another report, MDA acted as a promoter of thyroid tumors in rats. °... 

Thyroid follicular cell adenomas were increased in female mice treated with TBA, but this result lacks any independent supporting evidence from a number of studies in mice and rats. There was no evidence for a hepatic effect of TBA within this mouse carcinogenicity study therefore, no internal evidence exists for a hormonal mechanism of thyroid follicular cell induction. No thyroid neoplasms were increased in the carcinogenicity studies of MTBE. 

LOEL 250 mg/kg/day (mice) 125 mg/kg/day [10, 11] (rats) hepatocellular hypertrophy NOEL 10 mg/kg/day increases in liver and [1] kidney weights, increases in the incidence of hepatocellular hypertrophy, increases in thyroidparathyroid weights, hypertrophy and hyperplasia of the thyroid high incidences of trace-to-mild chronic nephritis in kidneys of male rats and increased pigmentation of the renal tubules in female rats LOAEL = 312 mg/kg/day (rats) 125 mg/kg/day [10, 11] (mice) hepatocellular neoplasms and adenomas or adenocarcinomas of the liver mononuclear cell leukemia adenomas or hyperplasia of the renal tubular cells in exposed male rats follicular cell adenomas or carcinomas of the thyroid in exposed female rats and female mice alveolar/bronchiolar adenomas or carcinomas in male mice 52 mg/kg Paroil intestinal activities of aryl [13] hydrocarbon hydroxylase (increase), UDP-glucuronosyltransferase (decrease) and epoxide hydrolase (increased)... 

A major breakthrough in the treatment of lymphoid malignancies was the discovery of monoclonal antibody activity, especially that of rituximab. Rituximab was the first monoclonal antibody approved by the U.S., FDA for the treatment of relapsed follicular lymphoma (1), and it has now been extensively used for the treatment of various lymphoid neoplasm which express CD20 antigen. Its efficacy has been also demonstrated against diffuse large B-cell lymphoma when administered as a combination regimen such as rituximab plus CHOP (R-CHOP) chemotherapy (2). 

Interferons are proteins or glycoproteins that are produced either by animal cells or plant cells in response to stimuli or DNA recombinant technology. These drugs are active against malignant neoplasms and have immunomodulating effects. These are useful in chronic hepatitis B, hepatitis C, hairy cell leukemia, myeloid leukemia, follicular lymphoma, carcinoid tumor, multiple myeloma, renal cell carcinoma, multiple sclerosis, chronic granulomatous diseases, blood disorders, common cold, herpes simplex, inflammatory bowel disease, and leishmaniasis. 

CD21 is a useful marker to identify neoplasms of follicular dendritic cells. The antigen density on dendritic reticulum cells is fairly high however, the same antigen is expressed at low levels on mantle zone B cells, which makes an excellent low-level control. 

The same t(14 18)(q32 q21) translocation described in the follicular lymphomas has been also identified in 15-35% of diffuse large B-cell lymphomas, a part of which seems to be transformed from the follicular lymphoma after the accumulation of other genetic abnormalities, in these cases the presence of the t(14 18) translocation indicates a poor prognosis. The overexpression of bd-2 is also found in many other lymphoid, myeloid and solid neoplasms. It is important to mention that the expression or the overexpression of bd-2 is not equivalent to the presence of the t(14 18) translocation-specific follicular lymphoma as it is expressed in many normal cells and in different tumors. The bd-2 is normally expressed in breast epithelium and many non-neoplastic lymphocytes including the small lymphocytes of mantle and marginal zones as well as thymus and many T-cell populations. Furthermore, bd-2 is frequently expressed in many soft tissue tumors such as solitary fibrous tumor, synovial sarcoma and rhabdomyosarcoma in addition to breast carcinoma and many lymphoma types as CLL and marginal cell lymphoma. 

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