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Biomedical subjects

Z Trizna

Publications and source records attributed to Z Trizna.

At least 37 records · Page 2Linked to original sources
PubMed1994

Mutagen sensitivity as a risk factor for second malignant tumors following malignancies of the upper aerodigestive tract.

BACKGROUND: Second malignant tumors in patients successfully treated for an initial cancer of the upper aerodigestive tract are an important cause of morbidity and mortality. Biologic markers capable of identifying high-risk subgroups of patients who could be targeted for intensive clinical surveillance, therefore, have immense therapeutic and prognostic relevance. We previously demonstrated in a pilot study of 84 patients with cancers of the upper aerodigestive tract that mutagen sensitivity was a significant predictor of risk of developing second malignant tumors. PURPOSE: We extended the study to include 278 patients diagnosed with previously untreated cancers of the upper aerodigestive tract from 1987 to August 1993. METHODS: For each patient, base-line (pretreatment) mutagen sensitivity was measured in vitro in 50 metaphases established from peripheral lymphocyte cultures. Patients with an average of more than 1 chromosomal break/cell were deemed mutagen hypersensitive. Cox proportional hazards analysis was used to predict the risk of developing second malignant tumors associated with mutagen sensitivity. RESULTS: Overall, 44% of the case group exhibited mutagen hypersensitivity. There were no differences in the distribution of mutagen hypersensitivity by site, sex, stage of disease, or smoking status. There were 17 synchronous and 11 metachronous cancers, of which 15 (54%) were smoking-related malignancies. Sixteen (13.1%) of the mutagen-sensitive patients developed second malignant tumors, compared with 12 (7.7%) of the nonsensitive patients. The mean break/cell value (+/- SD) for patients developing second malignant tumors was 1.17 (+/- 0.54), compared with 0.98 (+/- 0.44) for patients with only one cancer (P = .04). Mutagen hypersensitivity conferred a relative risk of 2.67 (95% confidence interval = 1.22-5.79) of developing second malignant tumors. CONCLUSIONS: Mutagen hypersensitivity increases the risk of developing second malignant tumors. IMPLICATIONS: Future research should focus on the molecular mechanisms underlying mutagen sensitivity.

Adult↗
PubMed1994

Epidemiology, biology, and chemoprevention of aerodigestive cancer.

Cancers of the aerodigestive tract are a major cause of worldwide morbidity and mortality. Long term survival rates for these epithelial cancers have not improved substantially in the past 20 years despite intensive efforts to improve the prevention and therapy of these diseases. Therefore, new approaches are needed. One new investigative approach is chemoprevention, the chemical prevention of cancer. Chemoprevention studies in the upper aerodigestive tract have focused on the reversal of premalignant lesions and the prevention of second primary tumors. These chemoprevention efforts have resulted from an understanding of the multistep nature of epithelial carcinogenesis and the diffuse epithelial injury that results from carcinogen exposure. Ongoing research efforts are attempting to define these processes. The interaction between carcinogen exposure and host susceptibility in the development of cancers of the aerodigestive tract is being evaluated (e.g., with an assay of chromosomal sensitivity to the clastogen bleomycin). This review discusses several new aspects of the epidemiology, biology, and chemoprevention of aerodigestive tract carcinogenesis.

Biomarkers, Tumor↗
PubMed1993

In vitro protective effects of chemopreventive agents against bleomycin-induced genotoxicity in lymphoblastoid cell lines and peripheral blood lymphocytes of head and neck cancer patients.

The protective effects of ascorbic acid (AA), n-acetyl-l-cysteine (NAC), alpha-tocopherol acid (ATA), alpha-tocopherol-acid succinate (TAS), and 13-cis-retinoic acid (CRA) on mutagen-induced chromosomal breakage were studied. Mutagen-sensitivity was determined by the bleomycin assay in human lymphoblastoid cell lines (LCLs) and cultures of peripheral blood lymphocytes (PBLs) from head and neck cancer patients. Preincubation with chemopreventive agents statistically significantly decreased mutagen-induced chromatid breakage in LCLs and PBLs in a dose-related manner. As the concentration of the agents was increased in tenfold increments in the study range, mean breakage rates were reduced by 3.0 to 7.7% in LCLs and by 6.0 to 11.1% in PBLs. The effective concentrations are comparable to those achieved in clinical applications and found in human dietary studies. A similar phenomenon in vivo, if identified, may explain the differences in occurrence of head and neck and other cancers between populations with different dietary habits. The bleomycin assay may be used for studying compounds with presumed chemopreventive properties.

Acetylcysteine↗
PubMed1992

Experience with the modified pectoralis major myocutaneous flap.

Results of 75 reconstructions with a modified pectoralis major myocutaneous flap are described in patients with advanced (stages III and IV) head and neck tumors between 1982 and 1986. The course of the supplying thoracoacromial artery was determined with angiographic studies and was found to follow the middle clavicular line in most cases. The pectoralis major muscle was mobilized up to its acromial attachment, which made the bridging of considerable distances possible between the site of the removed tumor and the donor site. The bulk of the pedicle was reduced at the same time without endangering the safety of the blood supply of the pectoralis major myocutaneous flap. The flaps were viable in the 70 evaluable patients. Partial necroses were observed in three cases. Postoperative fistulas were encountered in 13 patients (surgical closure was necessary in three). Reconstruction with the pectoralis major myocutaneous flap is a safe and versatile procedure, yielding good clinical and functional results in patients with advanced head and neck tumors.

Adult↗
PubMed1992

Pentamidine isethionate is negative in tests for microbial mutagenicity and chromosomal breakage in vitro.

Pentamidine isethionate, a drug used for the treatment of Pneumocystis carinii pneumonia in AIDS patients, was assayed for mutagenicity in five strains of Salmonella typhimurium and for clastogenicity and mutagen-induced chromosomal breakage in five human lymphoblastoid cell lines. The mutagenicity assay employed both repair-deficient and repair-positive strains without and with the addition of rat liver S-9. There was no indication of a mutagenic response in any of the strains of Salmonella. Chromosomal breakage was measured in lymphoblastoid cell lines, both in the absence and presence of bleomycin. Following 2, 5 and 24 h of treatment, pentamidine alone did not induce clastogenicity, nor was there an increase in chromosomal breakage when the cell lines were treated with bleomycin simultaneously with, or 22 h prior to, the addition of pentamidine. From these data it can be concluded that pentamidine is not mutagenic or clastogenic in the two assays employed in this study.

Animals↗
PubMed1992

Anticlastogenic effects of 13-cis-retinoic acid in vitro.

The anticlastogenic effects of 13-cis-retinoic acid were studied in four human lymphoblastoid cell lines and in primary lymphocyte cultures derived from the peripheral blood of 11 study subjects. Cells were pre-incubated with 13-cis-retinoic acid in the concentration range of 10(-8)-10(-5) mol/l for 24 h and the numbers of chromatid breaks per cell induced by bleomycin were determined. The presence of 13-cis-retinoic acid decreased the number of breaks per cell by 13.0 to 59.5% in lymphoblastoid cell lines and by 0 to 57.4% in primary lymphocyte cultures (in the concentration ranges of 10(-8)-10(-6) mol/l and of 10(-8)-10(-5) mol/l, respectively). Regression analysis showed that there was a statistically significant correlation between the presence of 13-cis-retinoic acid and protection against bleomycin-induced clastogenicity. These data give additional information to the knowledge of possible chemopreventive mechanisms of action of 13-cis-retinoic acid.

Antimutagenic Agents↗
PubMed1992

Hereditary and environmental factors associated with risk and progression of head and neck cancer.

The familial occurrence of head and neck cancers supports the role of heredity in this disease group. The roles of environmental and genetic factors are difficult to separate. There are several well-characterized entities, however, that are associated with risk and prognosis of head and neck cancer, including Lynch-II syndrome, Bloom syndrome, Fanconi's anemia, xeroderma pigmentosum, ataxia telangiectasia, and Li-Fraumeni syndrome. Mutagen-induced chromosomal damage is associated with an increased risk of multiple primary neoplasms and upper aerodigestive tract cancers. A possible reduction of genotoxicity, mediated by micronutrients, was demonstrated in vitro. Sister chromatid exchanges and micronuclei are useful exposure and disease markers. Metabolic changes (acetylation, DBQ phenotype, and the AH locus polymorphism) have been found to be associated with cancer of the upper aerodigestive tract. Most associations between histocompatibility antigens and solid tumors are relatively weak, probably because of the masking effects of environmental factors. Infections by HPV, EBV, and HSV have a causative or predisposing role in several types of head and neck cancer. Amplification and rearrangement of oncogenes may also play a role in carcinogenesis, and oncogene amplification may be associated with aggressive tumor behavior and unfavorable clinical prognosis. Ploidy of tumors seems to be an important determinant of survival and response to therapy.

Environment↗
PubMed1992

A radiation resistance factor in cultured Cloudman S91 mouse melanoma cells.

The gamma-ray survival of a radiation-sensitive amelanotic subclone of Cloudman S91 mouse melanoma, S91/amel, is increased by the presence in the tissue culture dishes of heavily irradiated cells from the same cell line (amel-HRCells) and from clonally related melanotic S91/I3 radioresistant cells (I3-HRCells). The D0 of the target S91/amel cells increases from 1.25 to 2.08 Gy in the presence of 60,000 heavily irradiated S91/amel cells per dish. The presence of I3-HRCells in dishes of target S91/I3 cells does not increase their radioresistance. Comparable numbers of I3-HRCells are more effective than amel-HRCells at increasing survival of target S91/amel cells irradiated with 3 Gy of gamma rays. Conditioned medium from the S91 melanoma cells also increases the radioresistance of S91/amel, but is not as effective as the HRCells. Unirradiated cells can condition the medium as effectively as irradiated cells. It is concluded that the radiosensitive mouse melanoma cell line is made significantly more resistant by a diffusible cellular factor(s) elaborated more proficiently by radiation-resistant cells.

Animals↗
PubMed1991

Effects of N-acetyl-L-cysteine and ascorbic acid on mutagen-induced chromosomal sensitivity in patients with head and neck cancers.

The protective effect of N-acetyl-L-cysteine (NAC) and ascorbic acid on mutagen-induced chromosomal breakage was determined using human lymphoblastoid cell lines as well as freshly cultured lymphocytes from patients with head and neck malignancies and healthy control subjects. Mutagen sensitivity was determined using the previously described bleomycin exposure assay. The toxicities of different concentrations of NAC and ascorbic acid, as well as both the preincubation and dose-dependent protective effects of these two agents, were analyzed. Both test drugs proved to be effective in diminishing mutagen-induced chromatid breakage in established lymphocyte cell lines. In freshly cultured lymphocytes, NAC given in doses ranging from 0.1 to 10 mmol/L decreased the number of mutagen-induced breaks per cell in a range from 23% to 73%, and ascorbic acid decreased chromosomal breakage by 21% to 58% in a dose range from 0.01 to 1 mmol/L. The results of this study demonstrate the protective effect mediated in vitro by both NAC and ascorbic acid against mutagen-induced chromosomal damage. A similar in vivo phenomenon may explain the differences in occurrence of head and neck cancer between populations with different dietary backgrounds.

Acetylcysteine↗
PubMed1991

Does melanin affect the low LET radiation response of Cloudman S91 mouse melanoma cell lines?

Melanin contains melanin-free radicals and can both absorb and produce additional free radicals and active oxygen species on exposure to various stimuli. Yet its role in the radiation responses of malignant melanoma has been little studied. In this report, three subclones of Cloudman S91 mouse melanoma clone PC1A varying in constitutive melanin content were compared with respect to killing by gamma irradiation. Radiation responses correlated with melanin content. The least melanotic line, S91/amel, was most sensitive and the most melanotic line, S91/I3, was most resistant. Curve fitting using the linear-quadratic model suggests that S91/amel is killed only by single event inactivations; S91/I3, only by double event inactivations; and S91/M1B, with intermediate melanin and radiation response, by both types of inactivations. Split dose experiments confirmed a lack of immediate split dose recovery in S91/amel and its existence in S91/I3. Potentially lethal damage and its repair could be demonstrated in both S91/amel and S91/I3. Double strand break (DSB) induction was evaluated as a function of gamma ray dose in DNA of S91/I3 and S91/amel, as well as in EMT6, a mouse mammary cancer line that lacks tyrosinase and melanin. The rates of induction were proportional to cellular melanization, i.e., the rate of DSB induction was greatest in S91/I3, least in EMT6. Levels of thioredoxin reductase (TR), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) were determined in S91/amel and S91/I3. TR was the same in both cell lines, while the other three enzymes were 3- to 4-fold lower in S91/amel.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Laryngeal lipoma.

We present a rare case of an intrinsic lipoma of the left false vocal cord in a 62-year-old man. The tumor was a manifestation of generalized lipomatosis. Successful endolaryngeal removal was accomplished.

Barium Sulfate↗
PubMed1990

[Possibilities of lymphoscintillography in head and neck surgery (II): results of clinical evaluation].

In order to determine the value of lymphoscintigraphy the clinical results were compared to the lymphoscintigraphic findings. The latter were further compared to the histological results and to the isotope activity of single lymph nodes. The examination was performed in 31 cases of head and neck malignancies before neck dissection (in 29 cases radical neck dissection was done because of palpable lymph nodes; in 2 further cases elective neck dissection was performed on the NO neck). Lymphoscintigraphy yielded evaluable results in 28 cases. Lymphoscintigraphy correlated with the clinical results in 21 cases. Lymphoscintigraphy, histopathology and clinical examination showed correlation in 19 cases. Further application of head and neck lymphoscintigraphy is warranted.

Head and Neck Neoplasms↗
PubMed1989

[Results following total laryngectomy at the Budapest Clinic of Head-Neck surgery].

The data on 356 laryngectomies during a 12-year period were analysed retrospectively. The operations were divided into three groups: group I, laryngectomy alone; group II, laryngectomy and secondary neck dissection; group III, one-stage laryngectomy and radical neck dissection. Most patients had advanced disease (stage III and IV: 54.5% and 23.9%, respectively). Supraglottic and glotto-supraglottic tumours were commonest (39.6% and 36.8%, respectively). The results of palpation, fine-needle biopsy and histology of the lymph nodes are compared. The mean survival time for the three groups was 53.4, 42.7 and 29.8 months, respectively, and the 5-year survival rates were 61.9%, 32.0% and 30.8%, respectively.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Phytophotodermatitis: a sometimes difficult diagnosis.

Phytophotodermatitis may not be diagnosed when a patient is seen with erythema and vesicles on the skin. However, with the appropriate medical history, the diagnosis of phytophotodermatitis is easily made. Arch Fam Med. 2000;9:1195-1196

Citrus↗
PubMedDate not supplied

Clastogenic interactions between lobeline sulfate and ethyl alcohol: a cytogenetic study.

The clastogenicity of lobeline and possible interactions between lobeline and ethyl alcohol were investigated in a mutagen-sensitivity assay on cultures of human lymphoblastoid cell lines. Lobeline (10(-6) M) and ethyl alcohol (1% and 2%) were added to the cultures alone or in different combinations prior to or simultaneously with bleomycin treatment. The number of chromatid breaks per cell served as the indicator of clastogenicity. Lobeline alone was not clastogenic, but there was a marked increase in genetic damage resulting from a coclastogenic interaction between lobeline and ethyl alcohol. These data emphasize the significance of interactions between compounds that may increase genotoxicity in cells exposed to mutagenic environments.

Bleomycin↗
PubMedDate not supplied

Protective effects of vitamin E against bleomycin-induced genotoxicity in head and neck cancer patients in vitro.

The quantitative protective effects of alpha-tocopherol acid and alpha-tocopherol acid succinate on mutagen-induced genotoxicity were studied in human lymphoblastoid cell lines and lymphocytes from cultures of peripheral blood. Both agents showed a dose-dependent protection both in lymphoblastoid cell lines and in lymphocytes of head and neck cancer patients. The concentrations used were in the phatmacologic concentration range of vitamin E. The protection against genetic toxic effects may be an important part of the cancer-protective effects of vitamin E.

Antimutagenic Agents↗