Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of the RET protooncogene tyrosine kinase (tk) by fusion with other genes is a frequent finding in papillary thyroid carcinoma. The tk domain of proto-RET can be fused either with the D10S170 gene generating the RET/PTC1 transforming sequence or with sequences belonging to the gene encoding the regulatory subunit RIA of c-AMP-dependent protein kinase A, thus forming the RET/PTC2 oncogene. We have previously shown that an inversion of chromosome 10, inv(10)(q11.2q21), is responsible for the generation of the RET/PTC1. Here we report that a chromosomal translocation, t(10;17)(q11.2;q23), juxta-poses the tk domain of the RET protooncogene, which resides on chromosome 10, to a 5' portion of the RIA gene on chromosome 17, leading to the formation of the chimeric transforming gene RET/PTC2. The finding of the transforming protein in primary tumor cell extracts supports the conclusion that RET/PTC2 activation plays a role in papillary thyroid tumorigenesis.
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PMID:A t(10;17) translocation creates the RET/PTC2 chimeric transforming sequence in papillary thyroid carcinoma. 751 46

Familial thyroid cancer can arise from parafollicular cells (familial medullary thyroid cancer) or from follicular cells (familial nonmedullary thyroid cancer). Familial medullary thyroid cancer may occur in isolation or as part of multiple endocrine neoplasia (MEN) type II syndromes. Genetic testing for a RET mutation on chromosome 10 is used to identify new family members who are gene carriers. Total thyroidectomy should be used in gene carriers without clinical disease before age 6 in medullary thyroid cancer and MEN type IIA, and as soon as the diagnosis is made in MEN type IIB after the first year of life. Those with clinical disease should have at least a bilateral central neck dissection. Modified radical neck dissection is recommended for patients when the primary tumor is 1.5 cm. A normal postoperative serum calcitonin level suggests that the operation has been curative. Physicians need to be aware of ethical and lifestyle issues related to patients with familial disease and their family members. Familial nonmedullary thyroid cancer occurs as a discrete entity or as part of other family cancer syndromes such as Gardner syndrome, Cowden disease, and other rare syndromes. Familial nonmedullary thyroid cancer almost exclusively includes patients with papillary or Hurthle cell cancers. These families appear to have more benign thyroid conditions. The gene (or genes) for familial papillary thyroid cancer is yet to be identified, whereas that for some Hurthle cells (TCO) has been mapped to chromosome 19p13.2. Familial nonmedullary thyroid cancer is somewhat more aggressive than its sporadic counterpart, but is less aggressive than medullary thyroid cancer. Total thyroidectomy and central neck dissection followed by radioactive iodine ablation and thyroid hormone suppression appear to be the most effective therapy.
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PMID:Familial thyroid cancer. 1114 85

Solid variant is a rare and poorly characterized variant of papillary thyroid carcinoma. In this study we analyzed 20 primary cases of the solid variant of papillary carcinoma found in a series of 756 papillary carcinomas operated at the Mayo Clinic between 1962 and 1989. The criteria for classification included predominantly (>70%) solid growth pattern of primary tumor, retention of cytologic features typical of papillary carcinoma, and absence of tumor necrosis. For each case of the solid variant, a control case of classical papillary carcinoma matched by age, sex, tumor size, and length of follow-up was selected. The follow-up ranged from 6 to 32 years. Two patients with the solid variant of papillary carcinoma (10%) died from disease 7 and 10 years after initial surgery, while another two patients (10%) are alive with lung metastases. In contrast, the control group had no cases with distant metastases or death from disease. Molecular analyses showed a similar prevalence of RET /PTC rearrangements in both groups. In conclusion, the solid variant of papillary carcinoma is associated with a slightly higher frequency of distant metastases and less favorable prognosis than classical papillary carcinoma. However, it should be distinguished from poorly differentiated thyroid carcinoma, which has a reported lower survival rate compared with the solid variant of papillary carcinoma.
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PMID:Solid variant of papillary thyroid carcinoma: incidence, clinical-pathologic characteristics, molecular analysis, and biologic behavior. 1171 36

Medullary thyroid carcinoma (MTC) is a rare disease, and most studies are either based on small numbers or multicenter studies with their inherent difficulties. Since 1995, a total of 440 patients with MTC underwent surgery in our clinic. A primary operation was performed in 188 patients (43% of 440). In 60 patients, the primary operation was performed because of a germline RET mutation ("prophylactic surgery"). Most (84%, 158/188) of the patients had pathologic calcitonin levels. Notably, MTC was found in almost 10% (3/30) of patients with normal calcitonin levels. However, all patients with lymph node metastases (LNMs) had elevated calcitonin levels. Total thyroidectomy (TTx) was performed in all patients. Lymph node dissection (LND) was performed at various extensions: one-compartment LND in 35% (66/188), three-compartment LND in 31% (58/188), and four-compartment LND in 29% (22/188). In general, lymph node dissection increased the likelihood of complications. LNM and distant metastases (DM) correlated with the extent of the primary tumor (pT category). The presence of LNM ranged from 17% (pT1 tumor) to 100% (pT4 tumor), whereas the presence of DM ranged from 0% (pT1 tumor) to 81% (pT4 tumor). Biochemical cure (normal calcitonin levels) was obtained in 72% (137/188) of patients. All 60 patients undergoing prophylactic surgery (tumor stage pT0/pT1) were biochemically cured. In contrast, only 60% (77/128) of the remaining patients were cured. The data suggest that primary surgery should be scheduled as soon as possible to treat patients at a node-negative stage. In the case of normal basal and elevated stimulated calcitonin levels, TTx and cervicocentral LND is recommended. If the basal calcitonin level is elevated, LND should include the cervicolateral compartment.
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PMID:Single center experience in primary surgery for medullary thyroid carcinoma. 1551 88

Medullary thyroid carcinoma (MTC) is a rare malignancy of the thyroid C cells. It occurs in hereditary (25% of cases) and sporadic forms, and aggressiveness is related to the clinical presentation (hereditary vs. sporadic) and the type of RET mutation present. In hereditary cases, early diagnosis makes preventative surgery possible. In established cases, thorough surgical extirpation of the primary tumor and nodal metastases has been the mainstay of treatment. Radioactive iodine, external beam radiation therapy (EBRT), and conventional chemotherapy have not been effective. Newer systemic treatments, with agents that target abnormal RET proteins, hold promise and are being tested in clinical trials for patients with metastatic disease.
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PMID:Current approaches to medullary thyroid carcinoma, sporadic and familial. 1713 4

Medullary thyroid carcinoma (MTC) is a rare malignancy of the thyroid C cells. It occurs in hereditary (25% of cases) and sporadic (75%) forms. Sporadic MTCs frequently metastasize to cervical lymph nodes. Thorough surgical extirpation of the primary tumor and nodal metastases by compartment-oriented resection has been the mainstay of treatment (level IV evidence). Surgical resection of residual and recurrent disease is effective in reducing calcitonin levels and controlling complications of central neck disease (level IV evidence). Radioactive iodine, external beam radiation therapy, and conventional chemotherapy have not been effective. Newer systemic treatments, with agents that target abnormal RET proteins hold promise and are being tested in clinical trials for patients with metastatic disease.
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PMID:Evidence-based approach to the management of sporadic medullary thyroid carcinoma. 1742 1

Medullary thyroid carcinoma (MTC) is an uncommon malignancy of the parafollicular C cells of the thyroid, with a propensity for early lymph node spread and distant metastasis. It is hereditary in approximately 25% of cases, involving specific point mutations of the RET proto-oncogene inherited in an autosomal dominant fashion. While European professional organizations have put forth calcitonin screening guidelines for earlier detection of MTC, the American Thyroid Association, which has published recent guidelines for MTC treatment, have not had a position on routine screening in the USA. Surgical extirpation of the primary tumor and involved lymph node metastases is the mainstay of treatment and the only chance for cure. Conventional systemic chemotherapies for metastatic MTC have been disappointing; however, newer agents which affect specific RET proteins and tyrosine kinase growth factor receptors show promise in phase 1 and 2 clinical trials.
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PMID:Current management of medullary thyroid cancer. 2021 15

CD133 (prominin-1) is a transmembrane glycoprotein expressed on the surface of normal and cancer stem cells (tumor-initiating cells), progenitor cells, rod photoreceptor cells and a variety of epithelial cells. Although CD133 is widely used as a marker of various somatic and putative cancer stem cells, its contribution to the fundamental properties of cancer cells, such as tumorigenesis and differentiation, remains to be elucidated. In the present report, we found that CD133 was expressed in several neuroblastoma (NB) cell lines/tumor samples. Intriguingly, CD133 repressed NB cell differentiation, for example neurite extension and the expression of differentiation marker proteins, and was decreased by several differentiation stimuli, but accelerated cell proliferation, anchorage-independent colony formation and in vivo tumor formation of NB cells. NB cell line and primary tumor-sphere experiments indicated that the molecular mechanism of CD133-related differentiation suppression in NB was in part dependent on neurotrophic receptor RET tyrosine kinase regulation. RET transcription was suppressed by CD133 in NB cells and glial cell line-derived neurotrophic factor treatment failed to induce RET in CD133-expressing cells; RET overexpression rescued CD133-related inhibition of neurite elongation. Of note, CD133-related NB cell differentiation and RET repression were mainly dependent on p38MAPK and PI3K/Akt pathways. Furthermore, CD133 has a function in growth and RET expression in NB cell line- and primary tumor cell-derived tumor spheres. To the best of our knowledge, this is the first report of the function of CD133 in cancer cells and our findings may be applied to improve differentiation induction therapy for NB patients.
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PMID:CD133 suppresses neuroblastoma cell differentiation via signal pathway modification. 2081 39

Neuroblastoma (NB) is the most common pediatric solid malignant tumor derived from the sympathetic nervous system. High-risk NB is still one of the most difficult tumors to cure, with only 40% long-term survival despite intensive multimodal therapy. The clinical presentation and treatment response of advanced NB, which results in relapse and a refractory state after a good response to the initial chemotherapy, suggests that cancer stem cells (CSCs) likely exist in NB tumors. Putative CSCs using primary tumor sphere formation from NB patients were reported previously, and several molecules will be elucidated from the tumor sphere to develop CSC-targeting therapies. Recently, our group reported that a CSC marker for several malignancies, CD133, and the stemness-related polycomb BMI1 have functions to repress NB cell differentiation. Depletion of CD133 or BMI1 effectively induced neurite elongation and marker molecules for differentiation in NB cells. Of note, CD133-related NB cell differentiation and RET (rearranged during transfection) repression were considerably dependent on p38MAPK and phosphoinositide 3-kinase (PI3K)/AKT pathways. Intriguingly, both CD133 and BMI1 also have a role in xenograft tumor formation and tumor sphere formation. These observations suggest that CD133 and BMI1 may be candidates for the development of CSC-targeting therapies for refractory NB patients.
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PMID:Role of stemness-related molecules in neuroblastoma. 2243 Mar 87

This multi centre observational cohort study gives a view about the occurrence, clinical and laboratory presentation, localization, histological type and genetic background of pheochromocytoma (PHEO) and paraganglioma (PGL) in Eastern Slovakia. It included 28 patients (18 women + 10 men), of which 23 were diagnosed to have PHEO (82,1%) and 7 patients (25%) suffered from PGL with retroperitoneal, inguinal/pelvic and mediastinal distribution. Arterial hypertension was the major symptom present in 86 % with slight dominance of paroxysmal form (58%). In 3 cases (10,7%), the diagnosis was gained after differentiation of adrenal incidentaloma in asymptomatic patients. Five patients (17,8%) were classified to have malignant form of the disease. 9 patients (32,1%) were confirmed to have hereditary form - five of them (17,8%) with familiar medullar thyroid cancer (FMTC) and mutations in RET gene classified as multiple endocrine neoplasia 2A and 4 patients (14,3%) with germline mutations of SDHB gene, respectively. There was found a relatively high occurrence of other co-morbidities: thyroid disease in 20 patients (71,4%), impairment of glucose metabolism in 11 patients (39,3%) and apart from FMTC, 4 patients (14,3%) suffered also from other malignancy. Together with a bigger size of the primary tumor (6,6 cm), higher concentrations of metanephrines and prevalence of extra-adrenal tumors, malignant and hereditary forms, we suppose genetic and environmental factors of Eastern Slovakia may play a role in the etiopathogenesis of the tumors.
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PMID:Analysis of pheochromocytomas / paragangliomas from Eastern Slovakia. 2358 19


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