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

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been recognized as important events in squamous cell carcinoma of the head and neck (HNSCC), suggesting involvement of both suppressor and mutator pathways. We analyzed 153 HNSCC with 8 Bethesda reference panel markers and 14 microsatellite markers selected from chromosomal regions known to harbor either tumor-suppressor genes or oncogenes. A combination of multiplex fluorescence-based polymerase chain reaction and automatic fragment analysis was performed. LOH was observed in 78% of all tumors. 2% to 17% LOH frequency was observed with Bethesda reference panel markers comparing to higher 8% to 48% LOH in chromosomal areas 3p, 9p, 11q, and 17p. LOH of 11q14.3 correlated with tumor grade. The proportions of high- and low-MSI tumors were 3% and 10%, respectively, but no mutation was identified in MLH1 and MSH2 mismatch repair genes. These results indicate the dominant role of the suppressor in comparison with the mutator pathway in HNSCC carcinogenesis.
 ...
PMID:Low microsatellite instability and high loss of heterozygosity rates indicate dominant role of the suppressor pathway in squamous cell carcinoma of head and neck and loss of heterozygosity of 11q14.3 correlates with tumor grade. 1449 93

Phosphoinositide 3-kinase (PI3-K) is a heterodimeric enzyme involved in the regulation of mitogenesis, apoptosis, cell adhesion, and motility. PI3-K was suggested as a protooncogene in human cancer. To determine the expression of PI3-K during cancerogenesis and tumor invasion of HNSCC, we investigated normal and dysplastic epithelium of the oral cavity, squamous cell carcinoma and lymph node metastasis by immunohistochemistry. The strongest immunoreactivity for p85alpha and p110alpha was found in invasive tumors and their metastases. Carcinomas in situ showed a focal positivity. Dysplasias and normal epithelium reacted predominantly negatively. The PI3-K inhibitor LY294002 inhibited proliferation and invasion of the HNSCC cell line CAL-27 and induced apoptosis in vitro. Our data suggest PI3-K as a marker of malignancy and tumor invasion. We suggest including PI3-K in the multistep carcinogenesis model of HNSCC. In addition, PI3-K is a potential target for pharmacological intervention.
 ...
PMID:[Phosphoinositide 3-kinase (PI3-K) expression. Tumorigenesis of epithelial carcinoma of the mouth]. 1476 10

Human papillomavirus type 16 (HPV16) is associated with squamous cell carcinomas of the head and neck (HNSCC) particularly from the Waldeyer's tonsillar ring. A causal role of HPV16 in carcinogenesis is linked to the activity of the viral oncoproteins E6 and E7 which inactivate the cellular tumor suppressors p53 and pRB, respectively. Lack of E6 expression in HPV16-positive HNSCC has been reported, in some cases caused by disruption of the E6 gene. We have examined the status of the HPV16 E6-E7 gene region in tumor and metastasis samples of 24 HNSCC patients employing genomic PCR. No cases with a disrupted E6-E7 region could be identified. Sequence analysis of the E6-E7 segments revealed three different HPV16 E6-E7 genotypes: the HPV16 prototype (6 of 21 cases), the E6 variant T350G (8 of 21 cases), and the E6-E7 variant A131G/C712A (7 of 21 cases). The E6 variants T350G and A131G have been associated with increased oncogenic potential in cervical cancer patients depending on host genetic factors. Their high prevalence in the HNSCC samples studied indicates that they may be important also in HNSCC development.
 ...
PMID:Human papillomavirus type 16 E6 and E7 genotypes in head-and-neck carcinomas. 1500 25

Head and neck cancer (HNSCC) includes squamous cell carcinomas of the oral cavity, pharynx and larynx. Approximately 38,500 cases of HNSCC are estimated to occur in the USA in 2004, with 11,000 deaths. HNSCCs represent about 3% of all malignant tumors in the USA. However, in other parts of the world, as India, Southeast Asia or Brazil, the disease is much more prevalent. The standard therapeutic approach, focused on surgery, irradiation and chemotherapy, alone or in combination, has been in part modified in the last 30 years, but the overall survival of HNSCC patients has not substantially improved. To characterize and thus identify high-risk mucosal areas and preclinical tumors, molecular abnormalities in head and neck carcinogenesis have been extensively studied. Metabolic aspects in head and neck carcinogenesis have been less extensively studied. Nevertheless, we know that metabolic alterations, often aspecific, are frequently associated with cancer. These may be secondary or may precede tumor development and favorite progression. In particular, based upon our results, a role for folate deficiency as a risk factor in head and neck carcinogenesis seems plausible. A chemoprevention protocol with folate is at present feasible and ethically correct and is already in progress at our institution. Homocysteine levels in cancer patients are probably largely affected by the HNSCC phenotype. An accumulation of homocysteine might reveal a genetic defect which is theoretically a target for pharmacological therapy, for example by antifolic drugs.
 ...
PMID:Hypofolatemia as a risk factor for head and neck cancer. 1560 14

The aetiology of squamous cell carcinomas of the head and neck (HNSCC) is multifactorial. Oncogenic human papillomaviruses (HPVs), a causative agent in uterine cervical cancer, have also been repeatedly detected in HNSCC, especially in squamous cell carcinomas of tonsils. Approximately half the HPV DNA-positive HNSCC contain detectable E6/E7 transcripts with wild-type p53, reduced pRb and overexpressed p16 in the tumours. HPV-16 is the predominant type and exists in episomal, integrated, or mixed forms. Tonsillar carcinomas have a remarkably higher viral load than carcinomas at other sites of the head and neck region. HPV-16 DNA has also been detected in tumour-free tonsils. Infection by oncogenic HPVs is a necessary but not a sufficient cause of cancers. Studies on the molecular mechanisms underlying HPV-associated carcinogenesis are difficult, because HPV is not easy to propagate in vitro. HPV-immortalised human tonsillar epithelial cell lines may provide an in vitro model to study co-factors for the HPV-associated tonsillar cancers and to test the effects of anti-viral and anti-tumour agents.
 ...
PMID:Human papillomavirus type 16 in head and neck carcinogenesis. 1594 78

The suppressors of cytokine signaling (SOCS) are inhibitors of cytokine signaling that function via the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. Recently, methylation of SOCS-1 and SOCS-3 has been implicated in the tumorigenesis of liver and lung cancer. This study was performed to elucidate the role of SOCS-1 and SOCS-3 in squamous cell carcinoma of the head and neck (HNSCC) and its precursor lesions. HNSCC of 94 patients and corresponding normal mucosa, lymph node metastases as well as 16 high- and 21 low-grade squamous cell dysplasias were studied by using methylation-specific PCR (MSP) for the SOCS-1 and SOCS-3 promoter after microdissection. The presence of SOCS-3 mRNA transcripts was confirmed by semiquantitative real-time PCR, and the SOCS-3 protein was analysed immunohistochemically. SOCS-3 hypermethylation was found in 85/94 HNSCC (90%) and in 10/16 high-grade and 9/21 low-grade dysplasias (63 and 43%, respectively). SOCS-1 promoter hypermethylation was detected in 10/94 HNSCC samples (11%) and in 2/16 high-grade and 1/21 low-grade dysplasias (13 and 5%, respectively). Lymph node metastases exhibited an identical methylation status as the primary tumors. Methylation of the SOCS-3 promoter correlated with downregulation of SOCS-3 transcripts and protein expression in these tumors and various cell lines. In the cell lines tested, SOCS-3 and SOCS-1 transcripts increased upon treatment with the demethylation compound 5-aza-2-deoxycytidine (5-AZA-DC). Overexpression of wild-type SOCS-3 in carcinoma cells with methylated SOCS-3 resulted in the induction of apoptosis and growth suppression as well as downregulation of STAT3, bcl-2 as well as bcl-xL. Our data suggest that promoter methylation and subsequent transcript downregulation of SOCS-3 transcripts and, to a much lesser extent, SOCS-1 are involved in the multistep carcinogenesis of HNSCC. During its involvement in tumor growth, restoration of SOCS-3 may hold treatment potential for HNSCC.
 ...
PMID:SOCS-3 is frequently methylated in head and neck squamous cell carcinoma and its precursor lesions and causes growth inhibition. 1600 69

E- cadherin is a member of the cadherin superfamily known as the main mediator of the cell- cell calcium dependent adhesion interactions. Research evidence also yields to this adhesion molecule an important role in carcinogenesis and tumor progression. This review focuses on the differential expression of E- cadherin in the various anatomic sites of the human body where HNSCC arises. Controversies in the results of various studies are discussed and possible prospects for application of all this developing knowledge to prognosis and therapy of the disease are briefly mentioned.
 ...
PMID:Role and expression patterns of E-cadherin in head and neck squamous cell carcinoma (HNSCC). 1676 12

In search of new targeted therapies for squamous cell carcinoma of the head neck (HNSCC), a better understanding of the carcinogenesis is of outmost importance. Recent studies show that not only genetic but also epigenetic alterations initiate the multistep process of tumordevelopment. Epigenetic changes lead to altered gene expression without alterations of the DNA sequence. The best characterized epigenetic change is the methylation of the promoter region of genes, especially of tumorsuppressor genes. The methylation of the promoter region blocks the promoter and therefore represses transcription. The loss of the gene products of tumorsuppressor genes leads to increased proliferation and decreased apoptosis. Methylation of tumorsuppressor genes was shown in precancerous lesions of HNSCC, which emphasizes the importance of methylation as an early biomarker. Several studies of tumor cell cultures show reactivated expression of proteins and as a result reduction of proliferation and induction of apoptosis after treatment with demethylating agentens. This presents a very promising new option for a targeted therapy.
 ...
PMID:[Role of epigenetics in the carcinogenesis of head and neck carcinomas - possible new targeted therapy?]. 1722 29

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most frequent cancer worldwide. Because HNSCC is largely acquired by environmental carcinogen exposure rather than through germ line mutations, there are no known familial forms of the disease in humans nor are there inbred rodent strains prone to spontaneous head and neck tumors. Transgenic animals with inactivation of tumor suppressor genes commonly mutated in human cases of HNSCC provide attractive models for studying the pathogenesis of head and neck cancer. p53 is the most frequently inactivated tumor suppressor gene in HNSCC. We used a chemical induction protocol in mice heterozygous for the p53 gene to evaluate how p53 inactivation contributed to head and neck carcinogenesis the mouse model. Metastatic squamous cell carcinomas developed in 100% of animals. Histopathologically, the tumors ranged from well to poorly differentiated and showed many molecular features of human HNSCC. Mice carrying only one p53 allele developed tumors with significantly reduced latency compared with wild-type controls (average, 18 versus 22 weeks). Metastatic cancer cells showed complete loss of p53 expression when compared with primary tumors. Transcriptional profiling showed not only distinct genetic differences between primary and metastatic tumors, but also when cancers from heterozygous null and wild-type animals were compared. Our results provide novel insights into the molecular genetics of tumor progression in head and neck cancer.
 ...
PMID:Loss of p53 expression correlates with metastatic phenotype and transcriptional profile in a new mouse model of head and neck cancer. 1742 50

The effect of preoperative radio chemotherapy on lymphatic drainage and intraoperative gamma probe-guided sentinel lymph node detection has yet not been investigated. In this study, we study 13 patients with SCC. Sentinel lymph node (SLN) imaging of the patients was performed using SPECT-CT. Special care was taken to use identical injection sites for both studies. Imaging comprised planar and SPECT, iterative reconstruction and were viewed with the co-registered CT image. The results were validated by comparison with the histological results of intraoperative gamma probe detection and histology of the completed neck dissection. Identical SLNs were found in 6/13 patients. In 2/13 cases SLN biopsies were false-negative. In 4/13 patients preoperative SLN imaging identified more/additional nodes than the initial imaging, whereas fewer nodes were seen in 3/13 patients. Neither the primary tumor site nor the TNM stage was predictive for changes in the lymphatic drainage pattern. No constant effect of irradiation could be demonstrated. Preoperative radio chemotherapy has an unpredictable influence on the lymphatic drainage pattern in HNSCC. Consequently, the intraoperative gamma probe-guided sentinel lymph node detection after radio chemotherapy does not reveal the SLN of carcinogenesis. Thus, we advise fused functional/anatomical imaging (SPECT-CT) before and after radiochemotherapy if the SLN concept is utilized in HNSCC.
 ...
PMID:Validity of sentinel lymph node (SLN) detection following adjuvant radiochemotherapy (RCT) in head and neck squamous cell carcinoma (HNSCC). 1799 97


<< Previous 1 2 3 4 5 6 Next >>