Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We searched for the presence of ganglioside reactive antibodies in sera of patients with differentiated thyroid cancer (DTC). Sera were screened by ELISA with plates coated with GM3(NeuAc), GM3(NeuGc), GM2, GM1, FucGM1, GD3, GD1a or GD1b gangliosides. Ganglioside reactive antibodies were detected more frequently in sera of patients with DTC than in sera of healthy persons, in keeping with the possibility of autoimmunization during carcinogenesis. Antibodies of IgM and IgG classes reactive with FucGM1 occurred most often. However, the infrequent occurrence of ganglioside reactive antibodies, their low titer and lack of correlation between their presence and clinical condition of the patients indicate that determination of these antibodies has no diagnostic value in DTC.
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PMID:Ganglioside reactive antibodies of IgG and IgM class in sera of patients with differentiated thyroid cancer. 1175 45

Thyroid cancer rates are three times higher in women than men during the period between puberty and menopause, suggesting that the etiology of thyroid cancer may be related to female sex hormones and reproductive function. However, the results from epidemiological studies have been mixed. To assess this hypothesis, data on menstrual history, pregnancy history, and exogenous hormone use were analyzed from a population-based, case-control study conducted in the San Francisco Bay Area. Of 817 incident thyroid cancer patients (cases), ages 20-74 years, who were diagnosed in 1992-1998 and 793 controls, identified by random-digit dialing and frequency matched to cases on age and race/ethnicity, 608 (74%) cases and 558 (70%) controls were interviewed. Of these cases, 544 were of papillary histology and included in the present analysis. Women who reported onset of menarche before age 12 or after age 14 were at about 50% increased risk for papillary thyroid cancer; however, this effect differed among age- and ethnic-specific subgroups. Among parous women younger than age 45, risk was elevated for several variables measuring recency of pregnancy. Risk was reduced for women who had ever used oral contraceptives [odds ratio (OR), 0.73; 95% confidence interval (CI), 0.52-0.97], but there was no trend with duration of use. Although it remains unclear how sex hormones influence thyroid carcinogenesis, these relationships warrant further investigation.
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PMID:Reproductive and menstrual history and papillary thyroid cancer risk: the San Francisco Bay Area thyroid cancer study. 1181 1

All authors integrating the known facts into a model of thyroid carcinogenesis concur that two main histotypes of thyroid cancer exhibit different routes of molecular development. RET rearrangements are an initiating event in papillary carcinoma, and simultaneously the most characteristic mutation for this type of cancer. They are followed by further, not well recognized, mutations. RAS mutations are regarded as a crucial event in the development of follicular tumors already at the adenoma step, while in papillary cancer they belong to the spectrum of secondary mutations, enabling tumor progression. Aberrant DNA methylation, causing loss of P16 tumor supressor gene, may be a common event in both types of cancer. Aneuploidy is seen much more frequently in follicular than in papillary cancer, which also exhibits a low rate for loss of heterozygosity and microsatellite instability. Mutations of the P53 tumor supressor gene are a common feature of undifferentiated thyroid cancers and could be responsible for their aggressive phenotype. RET rearrangements have been proposed as identifying fingerprints for irradiation induced thyroid cancer in children. Our own data speak against this hypothesis. We noted a high frequency of RET/PTC3 mutations in a group of Polish children with papillary thyroid carcinoma, regarded as sporadic cancer.
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PMID:Molecular changes in thyroid neoplasia. 1182 Jun 15

Both benign and malignant thyroid disease are well-established components of Cowden syndrome (CS), an autosomal dominant disorder characterized by multiple hamartomas and breast cancer that may be considered a phakomatosis. The susceptibility gene for CS is PTEN, a tumor suppressor gene on 10q23.3 that encodes a lipid phosphatase that lies upstream of protein kinase B (Akt). Interestingly, Carney complex is also a phakomatosis where multiple endocrine neoplasias are prominent and thyroid cancer might be a rare component. One of its susceptibility genes is the regulatory subunit of protein kinase A. Over the course of the last four years, investigators have found the increasing clinical spectrum of syndromes characterized by germline loss-of-function PTEN mutation. In addition to CS, subsets of such disparate syndromes as Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and possibly VATER with hydrocephalus and megencephaly with autistic features have been found to have germline PTEN mutations. Paradoxically, somatic intragenic PTEN mutations were rare in uncultured primary epithelial thyroid tumors, although hemizygous deletion occurred in 10-20% of thyroid adenomas and carcinomas. However, with subsequent study, it was discovered that epigenetic silencing of PTEN and perhaps inappropriate subcellular compartmentalization were two novel mechanisms of PTEN inactivation pertinent in thyroid carcinogenesis. Ectopic expression studies in vitro have borne out the importance of PTEN in the pathogenesis of epithelial thyroid neoplasias.
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PMID:Role of PTEN, a lipid phosphatase upstream effector of protein kinase B, in epithelial thyroid carcinogenesis. 1211 78

The molecular genetic basis of thyroid carcinogenesis is not well understood. Most of the existing models of thyroid cancer only rarely show metastases, and this has limited progress in the understanding of the molecular events in thyroid cancer invasion and metastasis. We have recently generated a mutant mouse by introducing a dominant negative mutant thyroid hormone nuclear receptor gene, TRbetaPV, into the TRbeta gene locus. In this TRbetaPV mouse, the regulation of the thyroid-pituitary axis is disrupted, leading to a mouse with high levels of circulating thyroid-stimulating hormone and extensive hyperplasia of follicular epithelium within the thyroid. As TRbeta(PV/PV) mice, but not TRbeta(PV/+) mice, aged, metastatic thyroid carcinoma developed. Histologic evaluation of thyroids of 5-14-month-old mice showed capsular invasion (91%), vascular invasion (74%), anaplasia (35%), and metastasis to the lung and heart (30%). Previous models of thyroid cancer have focused on genes that control initial carcinogenesis, but this model provides an unusual opportunity to study the alterations in gene regulation that occur with clinically relevant changes during progression and metastasis in a predictable fashion.
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PMID:Mice with a mutation in the thyroid hormone receptor beta gene spontaneously develop thyroid carcinoma: a mouse model of thyroid carcinogenesis. 1249 73

Activation of telomerase represents an early step in carcinogenesis. Increased telomerase expression in malignant thyroid tumors suggests that inactivation of telomerase may represent a potential chemotherapeutic target. The purpose of this study was to inhibit the protein component of telomerase, hTERT, in a human thyroid cancer cell line in vitro and in vivo using an antisense strategy. A 235-bp fragment of hTERT cDNA was subcloned, and sense and antisense hTERT expression vectors were constructed. These vectors were transfected into a human thyroid carcinoma cell line (FRO). Tumorigenic potential was determined by cellular growth assay, rate of apoptosis, anchorage-independent growth, and tumor growth in a nude mouse model. Significant down-regulation of hTERT expression was seen in the antisense transfected cells, compared with control and those transfected with the sense vector. A decrease in telomerase activity by TRAP assay was observed in the antisense hTERT cells but not in cells transfected with the sense hTERT construct. Inhibition of cell growth was observed after approximately 20 population doublings in the antisense-hTERT clones and was associated with an increase in the rate of apoptosis and a change in cellular morphology. Moreover, anchorage-independent growth was reduced in vitro, and tumor growth rate was diminished in vivo in the antisense hTERT clones. Inhibition of telomerase activity with antisense hTERT in human thyroid cancer cells is achievable and may represent a novel target to inhibit tumor growth.
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PMID:Antisense hTERT inhibits thyroid cancer cell growth. 1262 30

A sequence of genetic events characterized by deletion and expression of several oncogenes may lead progressively to tumorgenesis. The expression of certain oncogenes is believed to be related with thyroid carcinogenesis and tumor progression. We investigated immunohistochemically p53 tumor suppressor gene and c-fos oncogene expression in forty patients with thyroid cancer. Thyroid biopsies from twenty patients with benign thyroid diseases were also examined. The forty patients with thyroid cancer varied histologically; 24 with papillary carcinoma (60%), 12 with follicular carcinoma (30%), 3 with anaplastic carcinoma (7.5%) and one with medullary carcinoma (2.5%). The patients with benign thyroid diseases consisted of 10 with adenomatous goiter (50%), 7 with goiter (35%) and three with Hashimoto thyroiditis (15%). Individual p53 and c-fos expression was more prevalent in thyroid carcinomas compared to benign tumors (p=0.001 and p=0.04, respectively). A marked increase of p53 and c-fos coexpression was found (p=0.02) in patients with thyroid cancer and metastasis to the regional lymph nodes. Furthermore c-fos was overexpressed in only female thyroid cancer patients. In conclusion, p53 and c-fos are significantly overexpressed in thyroid cancer patients, indicating their role in the genetic mechanisms leading to thyroid tumorigenesis. This hypothesis is further supported by the observation that p53/c-fos coexpression was related with more advanced disease status.
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PMID:P53 and C-FOS overexpression in patients with thyroid cancer: an immunohistochemical study. 1268 75

Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia, thyroid cancer, soft tissue sarcomas, and many others. Although it has been known for a long time that radiation exposure to the cell results in extensive DNA damage, including double strand DNA breaks, the exact mechanisms of radiation-induced carcinogenesis remain unknown. Recently, a large increase in incidence of thyroid cancer was observed in children exposed to radiation after the Chernobyl nuclear accident. A high prevalence of chromosomal rearrangements involving the RET gene was found among these radiation-induced thyroid tumors. As a result of such rearrangement, a portion of the RET gene is fused with another gene, typically with the H4 or ELE1 . However, since the DNA targets of ionizing radiation are randomly distributed throughout the cell nucleus, the reason for predilection for the RET rearrangements in thyroid cells was unclear.
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PMID:Spatial positioning of RET and H4 following radiation exposure leads to tumor development. 1280 63

Together with thyroid cancer, cancer of the gallbladder is the only non-sex hormone-related cancer displaying a female preponderance, with incidence being 3-4 times more common among women. We carried out this study to evaluate the role of menstrual, reproductive and lifestyle factors in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of cholelithiasis was carried out. A detailed menstrual and reproductive history was illustrated beside detailed lifestyle history, in particular consumption of betel nut, tobacco and alcohol and smoking, odds ratio was calculated. Mean age of the patients with cancer was 51+/-1.2 years while it was 40.9+/-1.2 years for gallstones; 69% of cancer patients and 90% of gallstones patients were females. More than half of the cancer patients (53%) and 43% of the gallstone patients were illiterate. A past history of typhoid was present in 22% of cancer patients and 13% of gallstone patients, while 35% of cancer and 25% of gallstone patients were chewers, 18.1 and 9.9% were smokers, and 10% of cancer and 2% of gallstone patients consumed alcohol. Mean age of menarche was 13.4+/-1.2 years among female patients with cancer while it was 14.0+/-1.4 years for gallstone patients. Higher age at menarche (>13 years, OR 2.48, 95% confidence interval (CI) 1.16-5.3), higher number of childbirths(>3 births, OR 3.92; 95% CI 1.4-10.3), higher number of pregnancies (>3 pregnancies, OR 6.66, 95% CI 1.8-23.4), and higher age at last childbirth (>25 years, OR 2.97, 95% CI 1.04-8.5) were found to have significantly higher risk of developing gallbladder cancer. In conclusion, tobacco chewing and smoking are associated with increased odds of gallbladder cancer. Similarly early menarche, late menopause, multiple pregnancies and childbirth increased the risk of gallbladder cancer.
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PMID:Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer. 1288 78

There have been significant advances in our understanding of carcinogenesis at the molecular level over the last 25 years. Oncogenes are of major interest as part of our search for knowledge surrounding the aetiology of cancer. There are several oncogenes associated with thyroid cancer. Detailed investigation of the nature and function of these tumour genes has provided important insights into both the tumour biology and the complex biochemical pathways of normal cellular functioning. Our knowledge of oncogene biology offers the hope of better diagnostic, therapeutic and prognostic modalities in our fight against this and other common cancers. Development of specific thyroid tumour markers and gene therapy is now a realistic prospect to supplement our present armamentarium of surgery and radiotherapy. This review aims to outline the pertinent information gained so far from studies of these oncogenes and provides both clinical relevance and fuel for further interest amongst the ENT thyroid community in this exciting area of research.
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PMID:Oncogenes in thyroid cancer. 1296 38


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