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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prospective study was undertaken to determine the prevalence and histological correlates of human papillomavirus infection in the head and neck epithelium. Oral, pharyngeal, and laryngeal paraffin-embedded samples were analyzed by polymerase chain reaction with use of human papillomavirus E6 consensus sequence primers. Human papillomavirus infection was detected in 20 of 126 (15.9%) patients. Twenty-five of 230 (10.9%) samples contained human papillomavirus DNA. Papillomaviruses were detected in 15 of 131 (11.4%) head and neck squamous cell carcinomas, in 3 of 32 (9.4%) dysplasias, and 2 of 19 (10.5%) keratoses. The most commonly identified human papillomavirus in cancerous, precancerous, and keratotic lesions was type 16 (80.0% of the isolates). Five papillomas were shown to contain human papillomavirus type 6. No other lesion in 42 samples contained human papillomavirus. Our data are consistent with the hypothesis that infection with certain types of human papillomavirus contributes to head and neck cancer although this may be so only in a minority of cases. Human papillomavirus infection may play a role in the earliest stages of tumorigenesis, since papillomaviruses can be found in laryngeal premalignant and keratotic lesions, which are closely linked to tobacco use.
Diagn Mol Pathol 1995 Jun
PMID:Human papillomavirus infection in the malignant and premalignant head and neck epithelium. 755 Dec 92

Interleukin-2 (IL-2) gene therapy alone and in combination with the herpes thymidine kinase gene (tk) was used to evaluate immunological responses and antitumor effects in head and neck cancer. Established floor of mouth squamous cell carcinomas in C3H/HeJ mice were directly injected with recombinant adenoviral vectors carrying both therapeutic and control genes. One week after adenoviral gene transfer, only the animals treated with combination IL-2+tk or tk alone demonstrated significant tumor regression. Residual tumors were harvested for microscopic evaluation and immunohistochemistry staining, which revealed a predominance of CD8+ lymphocytes in the tumor beds of the animals treated with IL-2. To evaluate the systemic immune effects of IL-2, animals treated with single or combination gene therapy received a second site challenge with parental tumor cells or a heterologous but syngeneic sarcoma cell line. Mice treated with combination IL-2 and tk demonstrated a protective systemic immunity specific to the parental tumor cell line, whereas no systemic immune response was evident in mice receiving IL-2 alone. In a separate experiment, a range of concentrations of the adenovirus IL-2 vector were used to treat established tumors. Even with the maximal single-dose adenovirus concentration, IL-2 alone was ineffective as a single therapy. These results support the use of adenovirus-mediated gene transfer of IL-2 as an effective immunotherapy when used adjuvantly with the tk "suicide gene".
Mol Endocrinol 1997 Jun
PMID:The role of interleukin-2 in combination adenovirus gene therapy for head and neck cancer. 917 Dec 30

The p16INK4A (CDKN2A/MTS1) putative tumor suppressor gene encodes a cyclin dependent kinase inhibitor which plays an important role in the regulation of the G1/S phase cell cycle checkpoint. A high frequency of various p16 gene alterations were consequently observed in many primary tumors. P16 can be inactivated by different mechanisms: i) homozygous deletion, ii) methylation of the promoter region or iii) point mutation. In order to investigate p16 alterations in head and neck cancer (HNC) we analyzed 70 primary tumors of the larynx, pharynx and oral cavity including their corresponding normal mucosa for mutation inactivation by direct sequencing exon 2. We detected only one so far undescribed transversion G to T at position 322 (Asp108Tyr) and a known polymorphism (Ala148Thr) in five cases. The methylation status of the p16 promoter region was analyzed by an improved highly sensitive methylation-specific PCR protocol. P16 methylation inactivation was found in 16 of 55 cases (29%). Our data indicate that p16 point mutations in HNC are less frequent, but inactivation by methylation of the promoter region could be involved in genesis and progression of HNC.
Int J Mol Med 1999 Jul
PMID:Tumor suppressor gene p16 (CDKN2A) mutation status and promoter inactivation in head and neck cancer. 1037 39

P53 mutations are currently recognized as the most common genetic alteration in human tumors. The purpose of our study was to evaluate the significance and reliability of p53 genotyping in head and neck cancer as a possible marker permitting the prediction of tumor behavior and clinical outcome. P53 genotyping in our study refers to highly sensitive molecular screening in order to detect structural alterations in the nucleic acid sequence of the gene. Exons 2-11 and adjacent intronic regions were screened for mutations by direct genomic sequencing or by bi-directional dideoxyfingerprinting in 66 primary tumors of the larynx, pharynx and oral cavity. Alterations in the <hot spot region> of the p53 gene were detected in 36% (24 of 66) of the analyzed tumors, no mutation was found in our cohort outside exons 5-8. The frequency of p53 mutation had no correlation to the tumor stage or tumor site. The recurrence rate in patients with a p53 alteration was not significantly higher compared to patients without a p53 mutation in their primary tumors. Summarizing the results of our study only limited reliability of p53 genotyping as an effective concept for molecular testing of head and neck cancer was found.
Int J Mol Med 1999 Sep
PMID:P53 genotyping - an effective concept for molecular testing of head and neck cancer? 1042 79

Cigarette smoking is the major known risk factor for head and neck cancer. Tobacco promotes oxidative stress and enhances tissue levels of 8-hydroxyguanine (8-OH-G) in smokers. The presence of 8-OH-G does not impede replication but leads to an accumulation of G-->T transversions. Recently, the gene for human 8-oxoguanine DNA glycosylase 1 (hOGG1), an enzyme involved in the repair of 8-OH-G in humans, was cloned and mapped to chromosome 3p. In head and neck tumors, the hOGG1 gene locus is often targeted by loss of heterozygosity (LOH), and the spectrum of mutations in the p53 gene shows a bias in favor of G:C-->T:A transversions, as would be expected if HOGG1 repair functions were disabled. To test the involvement of hOGG1 in head and neck carcinogenesis, we had previously screened 56 tumors for LOH at 3p. From these tumors and two others, we selected 33 tumors demonstrating LOH for further mutational analysis of this gene. No somatic inactivating mutation was found in hOGG1. Polymorphisms involving intron 4 and exon 7 were present in 30% of the patients. A new polymorphism was identified in one patient in exon 6 and led to the amino-acid change G308E. Similar repair activities were found for the wild-type and exon 6-variant enzymes. Therefore, the involvement of hOGG1 in head and neck carcinogenesis is not strongly supported by this work.
Mol Carcinog 1999 Dec
PMID:Frequent allelic loss at chromosome 3p distinct from genetic alterations of the 8-oxoguanine DNA glycosylase 1 gene in head and neck cancer. 1056 2

It has been suggested that Helicobacter pylori (H. pylori) infection might be associated with not only gastric ulcers but also gastric malignancies. Recently, it was reported that the Streptococcus anginosus (S. anginosus) DNA sequence was found in DNA samples extracted from esophageal cancers. Because smoking and alcohol abuse are regarded as risk factors for both esophgeal cancer and head and neck cancer, infection of S. anginosus might be associated with carcinogenesis of head and neck cancer. To investgate the involvement of S. anginosus infection in head and neck cancer, we analyzed 217 DNA samples prepared from head and neck squamous cell carcinomas. We performed PCR analysis with S. anginosus-16S ribosomal DNA-specific primers, and Southern blot analysis. For detection of S. anginosus in the oral and pharyngeal cavities, we used oropharyngeal bacteriological culture and PCR analysis of gingival smears of the patients. By PCR analysis, the S. anginosus DNA sequence was found in 217 out of 217 (100%) DNA samples obtained from head and neck cancers. By Southern blot analysis, positive bands were detected in 41 out of 125 (33%) samples. We could find no S. anginosus colony in oropharyngeal bacteriological culture dishes of 53 patients with and without head and neck cancer. On the other hand, we found the S. anginosus DNA fragment in 8 out of 8 DNA samples obtained from gingival smears by PCR analysis. These data indicate that the upper aerodigestive environment of the patients permitting S. anginosus infection was implicated in the carcinogenesis of head and neck squamous cell carcinoma.
Int J Mol Med 2000 Dec
PMID:Streptococcus anginosus in head and neck squamous cell carcinoma: implication in carcinogenesis. 1107 31

The aim of this work is detecting the loss of heterozygosity (LOH) and its relationship with the development and progression of head and neck cancer. Matched normal and tumor DNA from 81 patients with head and neck cancer were examined for LOH using six microsatellite repeat markers mapped to chromosomal regions 3p13, 6q13, 9p21, 11p15, 17p13.1, and 17q22. LOH frequency at a locus ranged from 21% to 55%. The highest frequencies were at 3p (41%), 9p (48%), and 17p (54%). Thirty-two of 81 tumor samples showed allelic loss at more than one region. Significant associations were found between LOH at 3p and 9p (P = 0.001), 9p and 11p (P = 0.03), and 9p and 17p (P = 0.007). LOH at 11p was frequent in tumors from the oral cavity (5/17), oropharynx (2/7), and hypopharynx (5/10), but absent in tumors from the larynx (0/11) (P = 0.02), and LOH at 17q was observed in tumors from oral cavity (10/30) and hypopharynx (3/9), but not in tumors from the oropharynx (0/10) or larynx (0/13) (P = 0.003). In addition to that, the occurrence of allelic losses at 9p and 17p strongly correlates to tobacco smoking (P = 0.03 and P = 0.006, respectively) and alcohol intake (P = 0.01 and P = 0.005, respectively). These results suggest that tumors from different sites have different LOH patterns and corroborate with epidemiological data implicating tobacco and alcohol in the etiology of head and neck tumors.
Diagn Mol Pathol 2000 Dec
PMID:Distinct chromosomal deleted regions defining different subsets of head and neck tumors. 1112 47

Genetronics Inc has developed a MedPulser and a needle array applicator that delivers electric pulses to tumors and induces a transient permeabilization. Used in conjunction with intratumoral injections of anticancer drugs, this form of therapy, termed electroporation therapy, allows for intracellular accumulation of cytotoxic drugs without the toxic side effects associated with systemic administration. Accrual of preclinical data of electroporation therapy with bleomycin has led to clinical studies in patients with cutaneous and subcutaneous tumors. In 1999, objective responses were reported in a phase II study involving 30 patients with head and neck cancer with minimal side effects [328332]. Other indications for this form of treatment include liver and pancreatic cancers, Kaposi's sarcoma and melanoma [273388,290144]. Genetronics Inc and Ethicon Endo-Surgery (Johnson & Johnson Development Corp) are reviewing all clinical data from phase II studies prior to the initiation of a pivotal clinical trial in head and neck cancer.
Curr Opin Mol Ther 2000 Apr
PMID:Technology evaluation: electroporation therapy, Genetronics Inc. 1124 43

The current delineation of the molecular basis of cancer provides a strong rationale to consider gene therapy approaches for cancer as a complement to other cancer therapies. Phase III trials focused on adenoviral vector-mediated delivery of wild-type p53 to compliment p53 mutations were recently initiated for head and neck cancer and ovarian cancer. Clinical testing of the tumor inhibitory gene E1A, delivered by synthetic vectors is ongoing. Positive clinical data from these clinical studies will establish the use of gene therapy as a component of the multimodal treatment for certain cancers.
Curr Opin Mol Ther 2000 Aug
PMID:Gene therapy: a molecular approach to cancer treatment. 1124 73

Cationic lipid-DNA complexes are being evaluated for local or systemic therapeutic gene transfer. These positively charged liposomes fuse with negatively charged cell membranes and deliver the enclosed plasmid and its encoded gene to target tissues. This system has relevance for delivering genes to both normal and damaged or malignant tissues including phagocytes, tumor cells, endothelium and possibly parenchymal cells. Among the approaches being actively evaluated is the delivery of immunostimulatory cytokine genes (such as IL-2, IFN alpha or IL-12) into tumors. It is hypothesized that the local cytokine release will attract or induce antitumor immune responses. Valentis, (formerly GeneMedicine), has developed a plasmid encoding human IL-2 complexed with the liposomal preparation of DOTMA and cholesterol and has initiated phase I studies of intratumoral injection in head and neck cancer patients. Other routes of administration (intravenous and intratracheal), cytokines (IL-2) and proprietary liposomal-DNA complexes are being evaluated in preclinical models.
Curr Opin Mol Ther 2000 Aug
PMID:Technology evaluation: gene therapy (IL-2), Valentis Inc. 1124 76


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