UMLS:C0677930 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0677930 (primary tumor)
20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Head and neck cancer remains a common cause of mortality and morbidity in the United States and throughout the world. In spite of advances in the management of patients with advanced disease, overall survival in this group remains poor. Furthermore, although cancer mortality is lower in patients with early-stage disease, treatment results in significant morbidity, and these patients also face the risk of developing a second primary tumor. Chemoprevention is an innovative approach to decrease overall cancer morbidity and mortality using substances that are capable of preventing cancer progression. Head and neck cancer is an excellent model for chemoprevention, as its biology is consistent with the two concepts important for the development of chemoprevention strategies: field cancerization and multistep carcinogenesis. Several classes of compounds have been evaluated in chemoprevention trials. The most frequently studied agents, the retinoids, were found frequently to induce remissions in patients with oral leukoplakia. Furthermore, retinoids prevented progression to malignancy in one randomized maintenance study. Other agents, including beta-carotene and vitamin E, have been found also to have activity in the management of oral leukoplakia. However, the clinical role of chemopreventive agents in reducing cancer mortality remains to be defined. Two studies, one in head and neck cancer and one in lung cancer, have shown the ability of retinoids to prevent the development of second primary tumors. Current large randomized trials are defining the effectiveness of these agents in reducing the mortality of aerodigestive tract tumors in individuals at high risk.
...
PMID:Biology and chemoprevention of head and neck cancer. 805 3

The incidence of breast cancer is 25-30% of all malignant female tumors and represents the highest rate of mortality. To define those breast cancer patients at higher risk several prognostic factors are routinally evaluated in the primary tumor. Among them, the presence and degree of tumor involvement in axillary lymph node is one of the most powerful prognostic indicator. However, around 30% of node negative patients (good prognosis group) have recurrences and die within the next 10 years from diagnosis. Therefore, there is a need for markers to better discriminate biologic differences in the primary tumors. The techniques of molecular biology are shedding new insight into the subcellular pathology of malignancy. The crucial events of carcinogenesis, tumor progression, and metastatic spread are coming into focus at a molecular level. In some tumors, these advances in the laboratory are beginning to have applications at the bedside. Recently, abnormalities in the copy number and expression of several genes have been correlated with prognosis of individual patients with selected types of cancer. Molecular biology laboratories can provide useful predictive information that can be used to influence decision on the selection of treatment and to estimate a better risk stratification. Among these new markers are: oncongene amplification and/or over-expression, growth factors, cellular proliferation rate and ploidy, estrogens induced proteins, expression of metastasis related molecules, drug resistance associated proteins, etc. In this article we attempt to present a brief evaluation of a new technology that promises to add greater precision in evaluating molecular tumor markers and we mention some of its clinical applications.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Molecular markers to predict the prognosis of breast cancer]. 829 33

It has become evident that retinoids control differentiation, embryonal development, and tumorigenesis. In animal models, skin tumorigenesis has been shown to be prevented by retinoids, which in this organ function as antitumor promoters in the two-stage system using 7,12-dimethylbenz(a)anthracene (DMBA) as the initiator, and 12-tetradecanoyl-phorbol-13-acetate (TPA) as tumor promoter. Even though pharmacological doses applied topically appear to inhibit tumor formation, we found that papilloma and keratoacanthoma growth required physiological concentrations of retinoic acid and that vitamin A deficiency was even more effective than excess retinoid in inhibiting SENCAR mouse skin tumorigenesis. In human beings, oral administration of retinoic acid after tumor resection was effective in inhibiting the appearance of new tumors on the skin of four patients with Xeroderma Pigmentosum, and was effective in preventing new primary tumor formations in patients treated for head and neck cancer. The newly-discovered nuclear receptors for retinoic acid function as transcriptional activators for several genes. In patients with acute promyelocytic leukemia presenting with a reciprocal translocation of chromosome 17 to chromosome 15, the breakpoint has been identified in the retinoic acid receptor alpha gene, which forms a fusion gene with a new gene termed myl, on chromosome 15. Treatment of the patients with retinoic acid causes complete remission of the APL. It also appears to generate cells that do not bear the translocation. Therefore, retinoids may well function as modulators of carcinogenesis both at the promotion level as well as by causing differentiation of neoplastically transformed cells.
...
PMID:Multiple mechanisms: the example of vitamin A. 830 28

The effect of the human papillomavirus (HPV) oncogenes E6 and E7 was examined in transgenic mice with a construct containing the human beta-actin promoter regulating HPV16 E6 and E7 open reading frames. In the sole line of mice that transmitted the transgene, neuroepithelial tumors appeared at 2.5 months of life, and by 10 months, 87 of 122 (71%) of the animals were dead from brain tumors. The most frequent type of tumor (74%) was an anaplastic neuroepithelial tumor associated with the ependyma of the third and fourth ventricles, which locally invaded adjacent brain tissue and spread for considerable distances along the ventricular surface. The other two types of tumor were well-differentiated choroid plexus carcinomas (26%) and rare pituitary carcinomas (8.7%). HPV16 E6 RNA and E7 oncoprotein expression were demonstrated in tumor tissue and primary cell lines derived from the tumors. Examination of two tumor suppressor gene products, the retinoblastoma protein and p53, known to bind to HPV16 E7 and E6 oncoproteins, respectively, showed both were expressed in the primary tumor cell lines. These data support a causative role for the HPV oncoproteins in epithelial carcinogenesis.
...
PMID:Neuroepithelial carcinomas in mice transgenic with human papillomavirus type 16 E6/E7 ORFs. 838 43

We have established three cell lines from keratinizing and nonkeratinizing cervical carcinomas with distinct growth properties in vitro and in vivo. Each cell line contained human papillomavirus type 16 DNA sequences, but the lines differed in the physical state of the viral genome present in the cells. A high copy number of episomal human papillomavirus type 16 DNA sequences was detected in the TC-140 line derived from a keratinizing cervical cancer. This cell line had an aneuploid karyotype, did not grow in soft agarose, and formed benign cystlike nodules in nude mice, similar in morphology to well-differentiated areas of the primary tumor. Only integrated human papillomavirus type 16 sequences were detected in the TC-146A and TC-146B lines established from a nonkeratinizing large-cell cervical carcinoma. These cell lines exhibited reduced sensitivity to transforming growth factor-beta 1 and produced invasive, but not progressively growing, tumors in nude mice. These cell lines should complement existing in vitro models of cervical carcinogenesis and provide useful tools for understanding the importance of virus integration in the transformation process as well as the cellular and molecular basis for tumor progression.
...
PMID:Analysis of the growth properties and physical state of the human papillomavirus type 16 genome in cell lines derived from primary cervical tumors. 839 73

Retinoids, which include natural vitamin A (retinol) and its esters and synthetic analogues, are the best-studied class of agents in chemoprevention. There are more than 4,000 different retinoids which have a wide spectrum of preclinical activities, structures, pharmacological profiles, tissue distributions, receptor specificities, and toxicities. A number of retinoids have significant activity in many in vivo experimental systems including skin, bladder, lung, breast and oral carcinogenesis. In clinical trials, several retinoids have achieved significant activity in the reversal of head and neck, skin, and cervical premalignancy, and in the prevention of second primary tumors associated with head and neck, skin, and non-small cell lung cancer. Since 1984, our group has conducted a series of clinical trials to explore the chemopreventive potential of 13-cis-retinoic acid (13cRA) in the aerodigestive tract. We have conducted two consecutive randomized studies in subjects with premalignant lesions of the oral cavity. These studies showed that high-dose 13cRA alone can achieve significant short-term reversal of oral premalignancy, and that high-dose followed by low-dose 13cRA can maintain suppression of oral carcinogenesis. Three other randomized trials have confirmed significant retinoid activity in this human carcinogenic system. We also developed a randomized, placebo-controlled trial of adjuvant high-dose 13cRA in patients with head and neck cancer. Second primary tumor development was significantly decreased in the 13cRA group, but 13cRA had no impact on primary disease recurrence or survival. This presentation will update the current status of clinical trials and correlative laboratory studies of potential intermediate endpoint biomarkers in retinoid chemoprevention of aerodigestive tract carcinogenesis.
...
PMID:Retinoids and chemoprevention: clinical and basic studies. 853 83

Mutation of the p53 tumor suppressor gene is the most commonly observed gene alteration in human cancers. In order to identify new prognostic factors and tumor aggressiveness in squamous cell head and neck carcinomas, we analyzed 50 node metastases and 28 primary tumors including 13 matched specimens for p53 alterations. Mutations were found in 54 (69%) tumors, 76% of which were missense, 9% were nonsense and 15% were microdeletions or microinsertions. Twenty-five mutations were transitions mostly G-->A (40%) and 20 were transversions mostly G-->T (25%) thus confirming the role of tobacco carcinogens in the induction of these mutations. For eight patients mutations were observed in matched primary tumors and metastases, indicating clonal dissemination of tumor cells in most of these carcinomas. Furthermore the incidence of mutations was not different in primary tumors and node metastases indicating that this gene alteration was not related to the metastatic dissemination. No correlation was found between mutation and clinical parameters, the 8-year survival rates were not different (log rank test: P = 0.49) in patients with and without mutation. There was a good correlation between p53 mutation and protein overexpression (Fisher's exact test: P < 10(-4). Interestingly, immunostaining was also observed in basal cells from normal mucosa and in early lesions adjacent to the primary tumor in 11/15 specimens irrespective of the presence of mutation in the corresponding tumors. p53 protein overexpression may therefore constitute a biomarker for early stages of carcinogenesis of the head and neck epithelium.
...
PMID:[High incidence of p53 mutations in primary and metastatic head and neck tumors. Frequent protein overexpression in normal epithelium]. 869 25

Tobacco-related upper aerodigestive tract cancer is a worldwide health problem. Clinical advances in surgery, radiation, and chemotherapy have shown only marginal improvement on the survival rate of these malignancies in the past two decades. The concept of multistage carcinogenesis and field cancerization, the high incidence of SPTs, and the promising results of chemopreventive agents especially 13 cRA to effectively reverse oral premalignancy and prevent SPTs indicate a new avenue to improve the outcome of these newplastic diseases. The study of second primary tumor prevention is too early to show any survival benefit in the treatment arm and toxicity of high dose 13 cRA is significant. The current prospective large scale phase III SPT prevention trial of low-dose 3 cRA may establish a new standard approach for the control of head and neck neoplasms. Identification of potentially useful panels of biomarkers as intermediate endpoints will undoubtedly reduce time and cost currently required to conduct chemoprevention trials.
...
PMID:Chemoprevention of head and neck cancer. 870 1

Autocrine stimulation of the type I insulin-like growth factor receptor (IGF-IR) by IGF-II is one mechanism that allows cancer cells to maintain unregulated growth and to resist programmed cell death (PCD). SH-SY5Y and SHEP cells are cloned human neuroblastoma (NBL) lines originating from a single primary tumor. SH-SY5Y cells, which express abundant cell surface IGF-IR and produce IGF-II, exhibit serum independent growth and resist PCD due to hypoxia and hyperosmolar conditions. In contrast, SHEP cells, which produce no IGF-II and express five-fold fewer IGF-IRs, die in serum-free media or following exposure to metabolic stressors. To better understand the roles of IGF-IR and its ligand, IGF-II, in NBL carcinogenesis, we stably transfected SHEP cells with either IGF-II or IGF-IR. Unregulated expression of IGF-II did not alter the growth characteristics of SHEP/human IGF-II transfectants. In contrast, overexpression of IGF-IR allowed SHEP/IGF-IR transfectants to survive in media supplemented only by IGF-II. IGF-IR abundance correlated in a graded fashion with resistance to PCD in response to three different death-inducing paradigms: mitogen withdrawal, hyperosmolar metabolic stress, and treatment with etoposide. Our results suggest that adjuvant therapy aimed at reducing IGF-IR abundance may enhance chemotherapy-coupled apoptosis in the treatment of NBL.
...
PMID:Insulin-like growth factor I receptor prevents apoptosis and enhances neuroblastoma tumorigenesis. 881 51

The loss or mutational inactivation of the RB1 tumor suppressor gene has been implicated in the development of a diverse group of human malignancies. However, the contribution of the RB1 gene alteration to human prostatic carcinogenesis has been poorly understood. Thus far, deletion of the promoter sequence and exon 21 from one primary tumor specimen and the alterations found in the cell line DU-145, are the only cases of RB1 mutations reported in human carcinoma of the prostate. This study was designed to determine whether alterations in the structure or expression of the RB1 gene occur in human prostate carcinoma, and to determine the nature of these changes and the frequency with which they occur. One hundred twelve primary prostate tumor tissues and four metastatic lesions were obtained immediately after surgical resection. The RB1 gene was characterized in 68 tumor DNA samples using Southern analysis and the PG3.8M or H3-8 probes. Band profiles were analyzed by scanning densitometry. Sixty-three tumor DNA samples were analyzed for defects in the RB1 promoter using polymerase chain reaction (PCR) and heteroduplex analysis. Alterations in the expression of exons 1-27 were analyzed in 79 primary and four metastatic tumor RNAs using RT-PCR. Three of 68 tumors were identified to have gross rearrangement of the RB1 gene or deletion of one allele. One of four stage D tumor specimens showed truncated RT-PCR products indicating an internal deletion of RB1 transcripts. In all, 14 of 83 (17%) specimens displayed abnormally low levels of RB1 mRNA expression. Furthermore, these alterations of RB1 expression showed a correlation with increasing tumor stage and grade. These results suggest alterations of RB1 mRNA expression occur more frequently in higher stages and grades of prostate cancer and, thus, may be contributing to the malignant progression of a subset of human prostate cancer.
...
PMID:Alterations of the retinoblastoma gene in human prostate adenocarcinoma. 883 74

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>