Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Successful treatment of MTC depends heavily on early diagnosis and treatment. Often, this is not possible for sporadic MTC; however, genetic testing for hereditary MTC makes this possible if genetic carriers have surgery before C cells undergo malignant transformation. All patients who have MTC should be tested for RET mutations, including putative sporadic cases. The leukocytes of suspected carriers and sporadic MTC cases should be tested for MEN2-associated germ-line mutations by polymerase chain reaction amplification of the appropriate RET gene exons, including 10, 11,13, 14, 15, and 16 (see Table I). When a RET mutation is found, all first-degree relatives must be screened to determine which individuals carry the gene. If these exons are negative, the other 15 should be sequenced because a small risk of hereditary MTC remains if no germ-line mutation is found. The probability that a first-degree relative will inherit an autosomal dominant gene for MTC from an individual who has sporadic MTC in whom no germ-line mutation is found is 0.18% . Patients who have MEN2B or RET codon 883 or 918 mutation should have a total thyroidectomy within the first 6 months of life, preferably within the first month of life. Patients who have 634 mutations, which account for approximately 70% of all MTC mutations, should undergo thyroidectomy by age 5 years. The recommendations for the timing of prophylactic thyroidectomy are not consistent for the less common mutations (see Table 2). There is a balance between performing prophylactic thyroidectomy earlier than at the youngest age at with MTC has been reported to occur for a specific RET mutation (see Fig. 3 and Table 2) and the complications of thyroidectomy, including permanent hypoparathyroidism and laryngeal nerve damage. Preoperative measurement of plasma free metanephrine and neck ultrasonography always should be done if the diagnosis of MTC is known preoperatively. Initial treatment of MTC is total thyroidectomy, regardless of its genetic type or putative sporadic nature, because surgery offers the only chance for a cure. Treatment with 1311 has no place in the management of MTC. Plasma CT measurements provide an accurate estimate of tumor burden and are especially useful in identifying patients who have residual tumor. Pentagastrin- or calcium-stimulated plasma CT testing is useful in identifying CCH or early MTC in carriers of RET mutations that are associated with late onset MTC. Pheochromocytoma may occur before or after MTC and is an important cause of mortality, even in young patients. HPT is an important aspect of MEN2A and requires surgery according to current guidelines for the management of primary HPT. Early thyroidectomy and appropriate management of pheochromocytoma clearly have modified the course of this disease, but more research is necessary in kindreds who have rare MTC mutations. Moreover, new treatments for widespread MTC are necessary because current chemotherapy agents offer little benefit. New drugs that lock the action of tyrosine kinase offer some hope.
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PMID:Diagnosis and management of medullary thyroid carcinoma. 1515 57

Medullary thyroid cancer is a rare, neuroendocrine, tumor. It arises from parafollicular or C-cells with the ability to produce and secrete different bioactive substances like calcitonin (TC) and CEA (1-5) TC is ideal tumor marker in early diagnosis, in patents' follow up and in evaluation of their treatment. TC determinations after ca/pentagastrine stimulation test give us even more accurate results and the procedure is used for biochemical family screening. MTC occurs as a sporadic tumor or in hereditary settings MEN 2A, MEN 2B and FMCT. Germ/line point mutations in RET proto/onkogene are responsible for tumor arise and inheritance of settings. Genetic screening provides information of these RET mutations in family members even before pathologic changes occur. These individuals with MEN 2A, 2B and FMCT characteristic RET mutations are almost certain to acquire MTC (95% penetrance) in their lives and are candidates for preventive total thyroidectomy (TT), with or without central neck dissection (CND). Surgery is still the treatment of choice for MTC and only C-cell hyperplasia and early stage of MTC can be cured. Prophylactic thyroid surgery eliminates the possibility of MTC but doesn't influence appearance of other diseases (PHEO, HPTH) of MEN 2 syndromes.
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PMID:Medullary thyroid carcinoma. Genetic screening and prophylactic thyroidectomies. 1517 67

Sequence alterations in the RET proto-oncogene are becoming increasingly important to clinical assessment of the malignant disease of the thyroid. A spectrum of mutations is necessary to establish comprehensive phenotype to genotype relationship relevant to diagnosis and therapy of thyroid malignancies. We aimed to append to the increasing database of these oncogenic lesions and, therefore, analyzed DNA from tumor tissue and constitutive DNA from a patient with thyroid carcinoma. Mutational screening and sequence characterization of the RET proto-oncogene was performed to include part of the intronic sequences. We report a germline sequence variant in DNA from the patient diagnosed with microfollicular thyroid carcinoma. The carcinoma presented not as fully developed medullar carcinoma (MTC) but as microfollicular carcinoma with tendency to evolve into MTC. We characterized the sequence variant located in the intron 10 of the RET oncogene as an A to G substitution denoted IVS10 + 4G. The described sequence alteration generates a chi-like sequence surrounded by several chi-like sequences with recombinational potential. Such alteration may be involved in the pathogenesis of the microfollicular carcinoma via genome destabilization through homologous recombination in the process of tumor progression. This result further substantiates the importance of the database correlating specific sequence variations in the RET gene with distinct disease phenotypes.
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PMID:Sequence variant in the intron 10 of the RET oncogene in a patient with microfollicular thyroid carcinoma with medullar differentiation: implications for newly generated chi-like sequence. 1557 15

In 1903, Erdheim described the case of an acromegalic patient with a pituitary adenoma and three enlarged parathyroid glands. Fifty years later, Underdahl et al reported 8 patients with a syndrome of pituitary, parathyroid, and pancreatic islet adenomas. In 1954, Wermer found that the syndrome was transmitted as a dominant trait. In 1959, Hazard et al described medullary (solid) thyroid carcinoma (MTC), a tumor that later was found to be a component of two endocrine syndromes. The first of these described by Sipple in 1961 comprised pheochromocytoma, MTC, and parathyroid adenoma. The second, described by Williams et al in 1966, was the combination of mucosal neuromas, pheochromocytoma, and MTC. In 1968, Steiner et al introduced the term "multiple endocrine neoplasia" (MEN) to describe disorders featuring combinations of endocrine tumors; they designated the Wermer syndrome as MEN 1 and the Sipple syndrome as MEN 2. In 1974, Sizemore et al concluded that the MEN 2 category included two groups of patients with MTC and pheochromocytoma: one with parathyroid disease and a normal appearance (MEN 2A) and the other without parathyroid disease but with mucosal neuromas and mesodermal abnormalities (MEN 2B). Later, additional nonendocrine conditions (von Recklinghausen neurofibromatosis and von Hippel-Lindau disease) were found accompanying other more recently described familial MEN syndromes, indicating that these diseases are very complicated disorders.
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PMID:Familial multiple endocrine neoplasia: the first 100 years. 1564 84

In our previous studies, we used global computational differential display of ESTs that belong to UNIGENE clusters and identified human sequences differentially expressed in human tumors, as well as a considerable amount of transcripts represented only in tumor-derived cDNA libraries. Most of the tumor-specific EST clusters are derived from the plurality of the tumor types originated in tissues of both ectodermal and mesodermal origin. We found that many of such tumor-specific ESTs do not contain long open reading frames and cannot be classified as protein-encoding genes. To experimentally assess patterns of expression of these EST clusters, we studied four of them in PCR experiments on Clontech MTC panels. The experimental data confirm the results obtained by in silico screening, i.e. tumor specificity of their expression. We suggest that a significant increase in the expression of non-coding RNA is a fundamental feature of cancer cells, and that such transcripts could serve as markers for the diagnosis or monitoring of human malignancies.
Tumour Biol
PMID:Experimental study of human expressed sequences newly identified in silico as tumor specific. 1574 68

The genetic basis of the sporadic form of medullary thyroid carcinoma, derived from "C" cells, is still poorly understood. Somatic mutations of RET proto-oncogene have been reported at a variable frequency ranging from 23% to 69%. The hypothesis that low penetrance factors, such as polymorphisms, might contribute to the phenotype of this neoplasm has been addressed in a few studies conducting to conflicting results. Herein, we studied 100 individuals (50 patients and 50 controls) aiming to compare the frequencies of G691S, L769L, S836S, and S904S RET polymorphisms observed in patients with respect to controls. Furthermore, meta-analysis of published studies including the present results was conducted. To test the contributory role of the above polymorphisms for the development of "C"-cell hyperplasia, we studied a group of 10 individuals selected for having a positive pentagastrin test despite the absence of a RET germline mutation. An over-representation of the G691S polymorphism, particularly in females, was observed in patients with respect to controls, although not reaching the level of significance. Allelic frequencies of the other three polymorphisms were not different in patients and controls. Results obtained in the admittedly small group of individuals with a positive pentagastrin test are unlikely to support a major influence of any polymorphism in the development of "C"-cell hyperplasia. The meta-analysis provided evidence for a significant association of the S691 allele with MTC (odds ratio 1.54, 95% confidence interval 1.12-2.12, p=0.008) and found no significant associations for the other polymorphisms.
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PMID:RET polymorphisms and sporadic medullary thyroid carcinoma in a Portuguese population. 1623 Jul 79

In this study, the alterations (amplification/rearrangement) of 3 D-type cyclins loci were analyzed by Southern blot in 5 dysplastic head and neck lesions and 79 primary head and neck squamous cell carcinoma (HNSCC) of Indian patients to understand the role of the cyclins in development of the disease. No alteration was found in the dysplastic lesions. Overall, 54% of alterations were found in bcl-1/CCND1 locus, whereas amplification was only found in CCND2 and CCND3 loci in 12% and 2% samples, respectively. In bcl-1/CCND1 locus amplification was the major type of alteration; however, rearrangement as well as coalterations had been seen in some samples indicating the common mechanism of activation of this locus in different types of tumors. In bcl-1 region, the breakpoint clustered in the MTC (major translocation cluster) region, whereas in CCND1 the breakpoint located near 3' end of the gene. The coamplification of CCND2 locus with bcl-1, bcl-1/CCND1, and CNND3 loci suggests cumulative effect of these genes in this tumor. The significant association was seen between bcl-1/CCND1 locus alteration with HPV prevalence and poor patient outcome indicating its importance as prognostic marker. This indicates that the genetic instability caused due to HPV infection may induce the alterations in the bcl-1/CCND1 locus, which will provide selective growth advantage to the specific malignant clones resulting poor prognosis of the disease.
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PMID:Genetic alterations (amplification and rearrangement) of D-type cyclins loci in head and neck squamous cell carcinoma of Indian patients: prognostic significance and clinical implications. 1653 63

The goal in managing patients who have MTC is to detect and surgically remove disease at an early stage. Tumor marker-based biochemical screening and DNA-based genetic screening have created the opportunity for effective prophylactic surgery in patients at risk for hereditary MTC. Complete surgical resection is critical for cure because cervical reoperation for persistent or recurrent disease benefits only select patients. With the advent of therapies that target the RET-activated pathways, new hope may be emerging for patients who have locally advanced or metastatic disease.
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PMID:Medullary thyroid cancer. 1688 2

Multiple endocrine neoplasia (MEN) is defined as concurrent neoplasia or hyperplasia in more than one endocrine gland. MEN is well known in humans and has also been reported in small animals. We report on a dog family of a mixed breed with Alaskan malamute as a major influence, where three members developed thyroid carcinomas and another dog had clinical signs mimicking the other three but without a confirmed diagnosis. The age of onset of the tumour was between 96-109 months. Clinical, biochemical and immunohistochemical examinations revealed that the affected individuals typically demonstrated symptoms including calcitonin positive thyroid cancer, hypothyroidism and chronic dermatitis. In addition, elevated serum calcium and multinodular adrenocortical hyperplasia were demonstrated in a single member. The diagnosis observed is similar to the familial form of medullary thyroid carcinoma (FMTC) in human. This is the first report of FMTC in dog. Up to 95% of FMTC and MEN2 is known to be caused by activating mutations in the RET gene. The dog Ret gene was analysed as a candidate in this pedigree. The complete dog Ret genomic sequence was predicted in silico. The lack of demonstratable Ret mutation suggests the involvement of alternative predisposing mutation in this pedigree. The unique occurrence of familial MTC makes this potentially an important model in further defining the genetic basis of MTC.
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PMID:A dog pedigree with familial medullary thyroid cancer. 1701 49

A novel microwave electrode with a cooled tip (FORSEA MTC-3 type, China) was devised to better enable microwave ablation of liver cancers. The efficacy of this technology was evaluated. The records of 160 patients (97 with hepatoma, 63 with metastatic cancer of the liver) who had undergone microwave ablation with this new device were reviewed. One-year survival in 86 patients whose follow-up had been more than one year was determined. Pre-operative and post-operative contrast-enhanced CT scans were performed to assess completion of therapy and the presence or absence of recurrent tumor. For patients with hepatoma, serum alpha-fetoprotein (AFP) levels were evaluated pre-operatively and, if elevated, post-operatively. A median two (range one to five) applications were required per session. All patients exhibited initial radiographic resolution of their lesions after therapy. The ablated areas were not enhanced in any phases of contrast CT scan. Eight patients required a second microwave therapy for recurrent tumor; two patients required a third treatment. Twenty-five patients with hepatoma had elevated AFP (104.2+/-22.5 ng/ml), which, after microwave ablation, recovered to normal or almost normal (24.6+/-3.6 ng/ml) (t = 2.1, p<0.05). There were no post-operative deaths. Complications included fever in three of four patients, successfully treated with indomethacin, elevated transaminases in four of five patients, requiring no treatment except for those with pre-operative ascites (who were dialyzed), pleural effusions in fourteen patients, only one of whom required drainage, and obstructive jaundice requiring drainage in two patients. The one-year survival rate was 91.9%. Microwave ablation with this novel cooled-tip electrode is safe, minimally invasive and effective. The tool may greatly expand the fraction of patients with liver cancer who might be candidates for microwave ablation.
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PMID:Microwave ablation with cooled-tip electrode for liver cancer: an analysis of 160 cases. 1992 3


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