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Biomedical subjects

B Rodu

Publications and source records attributed to B Rodu.

At least 37 records · Page 2Linked to original sources
PubMed1996

Declining cancer mortality in the United States.

BACKGROUND: The overall age-adjusted cancer mortality rate had been increasing in the United States for as long as such statistics have been kept. This trend was reversed and a decline in cancer mortality began in 1991. METHODS: Vital statistics of the United States provided annual age-adjusted mortality rates for all forms of cancer and for lung carcinoma. Information from the Surveillance, Epidemiology, and End Results Program was also used to evaluate the effects on mortality of declining 5-year cancer case fatality. RESULTS: The overall age-adjusted cancer mortality rate declined in each succeeding year from 1990 to 1995 for a total reduction of about 3.1%. A major reduction occurred in lung carcinoma, which declined by 3.9%. Other smoking-related cancers declined by about 2%. The 5-year case fatality declined by approximately 0.5% per year from 1950-1954 to 1986-1991 for forms of cancer for which lead-time bias could be largely excluded. CONCLUSIONS: Both cancer prevention activities, especially those directed against smoking, and improvements in medical care have produced an appreciable reduction in cancer mortality in the United States. The nature of these changes suggests that the now ongoing decline will be sustained for the immediately foreseeable future.

Humans↗
PubMed1996

Influence of GC and AT specific DNA minor groove binding drugs on intermolecular triplex formation in the human c-Ki-ras promoter.

We have used DNase I footprinting and gel shift assays to characterize the interaction of DNA binding drugs mithramycin, distamycin, and berenil with an intermolecular triplex formed by the human c-Ki-ras promoter. A purine-rich triplex-forming oligonucleotide (ODN) forms a stable intermolecular triple helix (triplex) with a homopurine (PR):homopyrimidine (PY) motif in the human c-Ki-ras promoter which contains a 22bp PR:PY region (-328 to -307). This triplex structure is comprised of 15 G.G:C triplets interspersed with 7 T.A:T triplets. Mithramycin binding sites in the human c-Ki-ras promoter encompass most of the triplex target site and three G-C-rich sequences downstream of this triplex-forming region. Mithramycin binding within the c-Ki-ras promoter completely abrogates triplex formation. Furthermore, the addition of mithramycin to pre-formed triplex by c-Ki-ras promoter displaces the major groove bound ODN. Five prominent distamycin binding sites are noted within the c-Ki-ras promoter including the triplex-forming site as well as A-T-rich regions upstream and downstream of the triplex site. Berenil does not bind within the triplex target sequence, and only one berenil binding sequence downstream of the triplex motif was present within the c-Ki-ras promoter fragment. Neither distamycin nor berenil prevents triplex formation, and, furthermore, the addition of either distamycin or berenil to the pre-formed triplex structure did not displace the major-groove-bound third strand. This study demonstrates that GC-specific and AT-specific minor groove ligands differentially affect the intermolecular pur.pur:pyr triplex. A possible biological significance of mithramycin interaction with intramolecular triplex is discussed.

Base Sequence↗
PubMed1995

Tobacco use and cancer. A reappraisal.

With approximately six million users, smokeless tobacco has received considerable scrutiny as a risk factor for oral cancer. We review the relationship between smokeless tobacco use, keratosis, and oral cancer. Several features of smokeless tobacco keratosis, including the natural history, clinical presentation, and biologic behavior, differentiate it from other leukoplakias that exhibit greater malignant potential. Previous research has demonstrated that the relative risk of oral cancer with smokeless tobacco use is 4.2, about half of the risk from smoking (relative risk = 10 to 15). Mortality data from populations with sustained high-frequency smokeless tobacco use do not support the mistaken prediction of an epidemic of oral cancer with increasing smokeless tobacco use. In fact, the risks of smokeless tobacco use compare so favorably with those of smoking that smokers who switch to smokeless tobacco reduce their risks for all tobacco-related illnesses including oral cancer. Although some criticize this proposal as less than an ideal solution for the nation's smokers, full adoption of this strategy would eventually save over 400,000 lives each year.

Humans↗
PubMed1994

Triplex formation by the human Ha-ras promoter inhibits Sp1 binding and in vitro transcription.

The central role of the ras oncogenes in the pathogenesis of a wide variety of human malignancies is well established. Toward developing specific transcriptional inhibitors of the human Ha-ras oncogene, we have designed oligonucleotides to target a region of the Ha-ras promoter (-8 to -28) which contains two of the three Sp1 binding sites essential for transcriptional activity. Gel mobility analysis and DNase I footprinting demonstrate that an oligonucleotide (HR21ap) forms a sequence-specific triple helix with its target site in an antiparallel orientation with respect to the purine-rich duplex strand through predominantly G*G:C triplets. Within the Ha-ras promoter, HR21ap binds exclusively to the proximal target Sp1 sites over a similar nontarget distal sequence which, like the target, contains a consensus Sp1 site. Protein binding assays demonstrate that triplex formation by HR21ap inhibits Sp1 binding to the Ha-ras promoter. Moreover, oligonucleotide-directed triplex formation arrests Ha-ras promoter-dependent transcription in vitro. The results presented here suggest that triplex formation by the Ha-ras promoter targeted oligonucleotide may provide a means to specifically inhibit transcription of this oncogene in vivo.

Base Sequence↗
PubMed1994

Necrosis in benign salivary gland neoplasms. Not necessarily a sign of malignant transformation.

Necrosis that occurs in a salivary gland neoplasm is usually considered to be an ominous sign, suggesting malignant transformation, particularly in lesions that have had no prior manipulation such as fine-needle aspiration. We describe five pleomorphic adenomas and two canalicular adenomas of salivary gland origin that exhibited necrosis, yet were otherwise benign. All lesions displayed a distinctive histopathologic pattern characterized by a narrow rim of viable tumor tissue at the periphery of the neoplasm combined with a diffuse central region that demonstrated apparent ischemic necrosis. No invasion of adjacent normal tissue was identified, and no recurrence or metastasis has been seen with these lesions. Caution should be exercised in the evaluation of salivary gland neoplasms with central necrosis to avoid misdiagnosis of all such lesions as malignant.

Adenoma↗
PubMed1994

The G-C specific DNA binding drug, mithramycin, selectively inhibits transcription of the C-MYC and C-HA-RAS genes in regenerating liver.

Expression of the c-myc and c-Ha-ras protooncogenes is dramatically increased in regenerating rat liver as an early response to partial hepatectomy. Nuclear runon transcription studies confirm that the increased c-myc and c-Ha-ras mRNA levels in regenerating livers reflect transcriptional activation of these genes. Mithramycin, a G-C specific DNA binding drug, prevents the increased transcriptional activity of c-myc and c-Ha-ras genes after hepatectomy but does not alter the transcriptional activity of the beta-actin gene. Continuous exposure of rats to mithramycin after hepatectomy prevents the increase in both c-myc and c-Ha-ras expression and blocks the increased cellular proliferation characteristic of regeneration. The delayed increase in c-myc and c-Ha-ras gene expression is associated with a delay in cellular proliferation. The inhibition of c-myc and c-Ha-ras transcription by mithramycin, the delay in cellular proliferation, and the ability of mithramycin to prevent protein binding to the c-myc promoter, suggest that the increased expression of these genes is a necessary component of liver regeneration.

Animals↗
PubMed1994

An alternative approach to smoking control.

The detrimental health effects of cigarette smoking, including the increased risk of cancer, cardiovascular disorders, and pulmonary diseases, are well established. Although most smokers express a desire to quit, 46 million Americans continue to smoke because of the nicotine addiction associated with the habit. The author, in this paper, describes the magnitude of the health risks related to various forms of tobacco use and proposes that smokeless tobacco be recommended as a cigarette substitute by persons who cannot stop smoking. This proposal is made because smokeless tobacco is associated with far fewer and considerably less serious health consequences than is smoking. Of primary concern is oral cancer, the annual incidence of which is estimated at 26 cases per 100,000 smokeless tobacco users. If all American smokers used smokeless tobacco instead, this would result in 12,000 cases of oral cancer per year. This is only 1/20 of all smoking-related cancers, less than 1/10 of smoking-related lung cancers, and less than half the number of oral cancers now attributed to smoking. A public health policy that recognizes smokeless tobacco as an alternative to smoking would benefit individuals confronted with the unsatisfactory options of abstinence or continuing to smoke.

Humans↗
PubMed1994

Assessing the nicotine content of smokeless tobacco products.

The nicotine content of 11 popular brands of smokeless tobacco--including moist snuff, plug and loose-leaf chewing tobacco--was analyzed. In general, moist snuff has the highest nicotine content and loose-leaf chewing tobacco has the lowest, with plug tobacco falling in the middle. Variability in nicotine content may affect smokeless tobacco use and should be considered when studying usage as a variable for adverse effects of ST use.

Analysis of Variance↗
PubMed1994

Strategy for achieving selective killing of carcinomas.

Carcinomas are malignancies derived from epithelial cells that frequently respond poorly to conventional chemotherapy. Selective expression or transduction of toxin genes to carcinomas, i.e. molecular chemotherapy, may offer important advantages over conventional chemotherapy. As one approach to developing a means of selectively expressing toxin genes, the transcriptional regulatory sequences of a gene expressed in multiple carcinomas were used to direct expression of the herpes simplex virus thymidine kinase (HSVtk) coding sequences. The secretory leukoprotease inhibitor (SLPI) gene was found to be expressed in lung, breast, oropharyngeal, bladder, endometrial, ovarian and colorectal carcinomas. The tissue-specific transcriptional regulatory sequences were isolated and used to construct a chimeric gene in which the SLPI sequences directed HSVtk expression. SLPI-expressing carcinomas were reduced in number by transduction of the SLPI-directed toxin plasmid plus ganciclovir, but the same treatment had no effect on a cell line that did not express SLPI. These results suggest that SLPI-directed therapeutic genes could be used for directing toxicity to carcinoma tissues, especially if combined with other targeting strategies.

Adenoviridae↗
PubMed1993

Quincke's disease: nonhereditary angioneurotic edema of the uvula.

We report two cases of Quincke's disease, an isolated form of angioneurotic edema involving the uvula that is induced by several factors, including foods, drugs, and inhalants. Although Quincke's disease has prominent oral manifestations, it has only rarely been described in the dental literature. The rapid onset and progression of the disorder, combined with the risk of respiratory compromise, may result in a serious medial emergency. Clinical manifestations include a nonerythematous swollen uvula, fullness in the throat, and signs of airway obstruction. A hereditary form of angioneurotic edema is associated with a biochemical defect; this must be differentiated from nonhereditary, localized forms such as Quincke's disease to determine appropriate treatment and predict prognosis. Clinical features and laboratory tests can distinguish hereditary angioneurotic edema from the nonhereditary form.

Adult↗
PubMed1993

Triplex formation inhibits HER-2/neu transcription in vitro.

Triplex-forming oligonucleotides (TFOs) have been shown to bind to target DNA sequences in several human gene promoters such as the c-myc oncogene, the epidermal growth factor receptor, and the dihydrofolate reductase genes. TFOs have been shown to inhibit transcription in vitro and gene expression in cell culture of the c-myc and other genes. The HER-2/neu oncogene, which is overexpressed in breast cancer and other human malignancies, contains a purine-rich sequence in its promoter, which is favorable for purine:purine:pyrimidine (R:R:Y) triplex formation. Although its function in the HER-2/neu promoter is unknown, this purine-rich site is homologous to a protein-binding sequence in the promoter of the epidermal growth factor receptor that is necessary for efficient transcription of this gene. We have shown that this sequence is a site for nuclear protein binding by incubation with a crude nuclear extract. We describe the formation of an interstrand triplex using a purine-rich oligonucleotide antiparallel to this purine-rich target sequence of the HER-2/neu promoter. Triplex formation by the oligonucleotide prevents protein binding to the target site in the HER-2/neu promoter in vitro. We have shown that this oligonucleotide is a potent and specific inhibitor of HER-2/neu transcription in an in vitro assay. The triplex target site contains a single pyrimidine base that does not conform to the R:R:Y triplex motif. In an attempt to abrogate the potentially destabilizing effects of this pyrimidine base on triplex formation, we have substituted an abasic linker for the pyrimidine residue in the triplex forming oligonucleotide. Triplex formation with the modified oligonucleotide appears to occur with approximately equivalent binding affinity. Triplex formation in the HER-2/neu oncogene promoter prevents transcription in vitro and may represent a future modality for specific inhibition of this gene in vivo.

Base Sequence↗
PubMed1993

New approaches to the diagnosis of oral soft-tissue disease of viral origin.

Molecular biology is changing the face of diagnostic medicine, and infectious diseases of the oral soft tissues are among the targets of these advances in biotechnology. As an illustration of these concepts, a PCR-based detection and typing system for human papillomaviruses (HPVs) will be discussed. A single "consensus" set of oligomeric nucleotide primers can be used to amplify a 571- to 594-base-pair region of the E1 open reading frame of HPV 6, 11, 16, and 18. These HPV types are commonly associated with preneoplastic and cancerous lesions of the genital, respiratory, and digestive tracts. PCR amplification yields single bands of similar size for these viruses by agarose gel electrophoresis. Digestion of the resultant products by the restriction endonuclease AccI yields distinctive and reproducible banding patterns by polyacrylamide gel electrophoresis (with ethidium bromide) due to their internal sequence diversity. The system is sensitive; without radioisotopes, it can detect and type HPV 18 in as little as 100 pg of DNA from HeLa cells. We have used it to confirm HPV in fresh-frozen tumors. Computer sequence analysis can be used to modify the system for the detection of new HPV types as they are characterized. Other applications of molecular-biology-based detection systems for infectious diseases of the head and neck region will be discussed.

Herpesvirus 2, Human↗
PubMed1992

Clinical evaluation of MGI 209, an anesthetic, film-forming agent for relief from painful oral ulcers associated with chemotherapy.

PURPOSE: This open-label, multicenter trial evaluated the efficacy of a mucoadherent, anesthetic medication (MGI 209) for relief from painful oral ulcers associated with cytotoxic chemotherapy. PATIENTS AND METHODS: Twenty-eight eligible cancer patients who had up to five discrete oral ulcers (total area < or = 5 cm2) completed this study. Mean age was 53.5 years (range, 21 to 81). Subjective assessments of oral discomfort before and after an orange juice pain challenge (OJPC), which was measured using a visual analog scale (VAS), and visual estimates of the amount of MGI 209 that remained on treated ulcers were collected at (1) baseline (before MGI 209 treatment); and (2) 30, 60, 120, and 180 minutes posttreatment. RESULTS: Most subjects had low VAS scores (4 or less), which was indicative of oral discomfort, at baseline before and after the OJPC. At 30, 60, 120, and 180 minutes after MGI 209 treatment, most subjects had high VAS scores before and after an OJPC compared with baseline scores, which was indicative of a substantial increase in oral comfort; these differences were statistically significant (P < .0001). Mean percent of MGI 209 estimated to remain on ulcers at the previously mentioned times was 93.7%, 90.3%, 79.6%, and 71.3% of the total amount applied, respectively. CONCLUSION: Benzocaine hydrochloride in combination with the protective, mucoadherent film-coating relieved discomfort for at least 3 hours even with exposure to an irritating beverage. MGI 209 treatment should allow patients with chemotherapy-induced oral ulcers to drink and eat with significantly diminished pain or no pain.

Adult↗