Metástasis incisional de carcinoma broncogénico tras linfadenectomía mediastínica transcervical extendida / Incisional metastasis from lung cancer after transcervical extended mediastinal lymphadenectomy

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Bronchogenic and alveologenic tumors in mice induced by N-nitrosopiperidine.

The aim of this study was to explore the histogenesis and carcinogenesis of pulmonary cancer induced by N-nitrosopiperidine (NPIP) in mice. NPIP is a form of N-nitrosamine found in tobacco smoke, which has been shown to be a genotoxic chemical as well as a mutagenic compound for inducing chromosome aberrations and severe clastogenicity. In this study, 80 BALB/C strain mice were injected with 0.2 mmol/kg NPIP intraperitoneally for 8 weeks, and experiments were conducted for a further 16 weeks. For the control group, 40 mice were injected with an equal volume of 0.9% NaCl. Pulmonary tissues and tumors in the NPIP-treated group were examined by light microscopy and transmission electron microscopy and compared with the control group at 4-week intervals. The mRNA levels of p53 (mutant), bcl-2, c-myc, ras, and subunits of telomerase - telomerase reverse transcriptase (TERT) and an RNA component, TR - were assayed by mPCR or RT-PCR. Twenty-two mice in the experimental group were found to develop pulmonary tumors, but none in the control group. All tumors found in the experimental group originated from alveolar type II epithelial cells. In addition, 6 of the 22 mice also developed tumors of bronchogenic origin. The expression of p53, bcl-2, c-myc, ras, and the subunits of telomerase were found to increase in all pulmonary tissues and tumors formed thereafter upon NPIP treatment. In summary, NPIP-induced mouse lung tumors exhibited morphological changes during carcinogenesis, which may be the consequence of overexpression of some genes associated with the development of carcinoma and changes in subunits of telomerase. This mouse model of lung tumor formation may be a useful tool to delineate the histogenesis and carcinogenesis of human pulmonary cancer.

Single- and multi-wall carbon nanotubes versus asbestos: are the carbon nanotubes a new health risk to humans?

Carbon nanotubes (CNT), since their discovery, have become one of the most promising nanomaterials in many industrial and biomedical applications. Due to their unique physicochemical properties, interest is growing in the manufacture of CNT-based products and their subsequent marketing. Since their discovery, the prospect of possible undesirable human health effects has been a focus of many scientific studies. Although CNT possess unique physical properties that include (1) nanoscale diameter, (2) a wide length distribution ranging from tens of nanometers to several micrometers, and (3) high aspect ratio, the fibrous-like shape and durability suggest that their toxic properties may be analogous to those observed with other fibrous particles, such as asbestos. The present study provides a summary of published findings on CNT bioactivity, such as the potential of CNT, especially of multi-wall carbon nanotubes (MWCNT), to activate signaling pathways modulating transcription factor activity, induce apoptosis, induce DNA damage, and initiate biological responses. Assessment of risks to human health and adoption of appropriate exposure controls is critical for the safe and successful introduction of CNT -based products for future applications.

Microscopic analysis of the chromium content in the chromium-induced malignant and premalignant bronchial lesions of the rat.

OBJECTIVE: Our previous studies demonstrated that the frequency of gene instability in lung cancer of chromate workers was very high, but the frequencies of the p53 and ras gene mutations were low. To clarify the carcinogenesis of chromate in the lung, we established a chromate-induced cancer model in the rat proximal airway and examined the relationship between chromium accumulations and the chromium-induced cancer and premalignant bronchial lesions of the rat. METHODS: Fifteen male, bred, 12-week-old Jcl-Wister rats were used. A pellet of strontium chromate were inserted into the bronchus of the rats. The rats were sacrificed 9 months after the pellet was inserted. We pathologically examined the region of the bronchi to which the pellet was attached. We quantified the amount of chromium accumulation in the bronchial lesions using a microscopic X-ray fluorescence analyzer. RESULTS: Of the 15 rats, 1 rat had a lesion of squamous cell carcinoma (SCC), 7 rats had carcinoma in situ (CIS) or dysplasia, 8 rats had squamous metaplasia, and 5 rats had goblet cell hyperplasia. The amounts of chromium accumulation in normal epithelium (n=24), goblet cell hyperplasia (n=14), squamous metaplasia (n=8), and dysplasia plus CIS plus SCC (n=9) were 500+/-1354, 713+/-1062, 941+/-1328, and 3511+/-4473 (mean+/-SD) counts/s/mA, respectively. The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium (Spearman's correlation coefficient by ranks, rs=0.454, P<0.01). CONCLUSIONS: The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium. Examining the genetic alterations of histologic changes in this model was helpful in elucidating the process of carcinogenesis of chromium in the lung.

3-Methylcholanthrene triggers the differentiation of alveolar tumor cells from canine bronchial basal cells and an altered p53 gene promotes their clonal expansion.

Alveolar type II cells arising in canine bronchial autografts following exposure to 3-methylcholanthrene (MCA) give rise to carcinomas of varying glandular and squamous growth patterns. To study the role of the tumor suppressor gene p53 in this process, sections from progressive lesions were immunostained for p53 protein; microdissected regions were screened for p53 mutations. Adjacent sections were examined for type II cell expression [cuboid cell shape, large roundish nucleus, cytoplasmic staining for surfactant protein A (SP-A)] and proliferating cell nuclear antigen expression. Evidence for an altered p53 function (nuclear staining, missense mutations) was found in most carcinomas of all histologic types and in all grades of bronchial dysplasia, but not in hyperplastic or normal bronchial epithelium. It was primarily associated with the hyperplastic type II cell populations present in the basal zone of the lesions. In addition, we found SP-A staining in hyperplastic (but not in normal) bronchial basal cells. These data suggest that MCA initiates type II cell differentiation through phenotypic selection (basal cells). Inactivation of the p53 gene promotes the clonal expansion of the type II cells into discernible populations of (squamous or glandular) alveolar tumor cells. This in vivo study is the first to show that p53 is involved in a specific pathway leading to bronchogenic carcinoma.

[Chemoprevention of bronchogenic carcinoma]. / Chemoprevence bronchogenního karcinomu.

Lung cancer is the leading cause of cancer-related deaths in many developed countries. Understanding its carcinogenesis is critical for the development of rational approaches to cancer prevention. The concept of chemoprevention is based on the idea that the diffuse injury of the respiratory epithelium results from chronic carcinogen exposure. Chemoprevention agents should reverse or suppress the development of premalignant and malignant changes by different mechanisms. In the future, the clinical application to risk groups of patients could lead to substantially decreased frequency of the lung cancer. The results of ongoing trials are eagerly awaited.

Histogenesis of adenosquamous bronchogenic carcinoma.

In our hamster lung cancer model studies, among 463 non-small-cell lung cancers (NSCLC), there were 47 adenosquamous neoplasms. In 24 of 27 lesions with diameters of less than 3.0 mm, the adenocarcinoma and the squamous cell carcinoma components arose as separate, spatially discrete lesions, but these were separate in only 7 of 20 lesions with diameters of 30 mm or greater. Co-infiltration of the components became more frequent as tumor size increased. The usual adenosquamous variety of NSCLC is likely a collision tumor, with each component possessing separate biological characteristics. Thus, future prognostically directed studies of this variety of NSCLC must recognize that these neoplasms have two components, each of which needs to assessed.

Bronchial carcinoma mortality in the German chromate-producing industry: the effects of process modification.

This study updates a 1982 report on mortality at two German chromate-producing factories. The main objective of the study was to establish whether the change-over to a production process using lime-free conversion of chromite ore, thus eliminating the formation of calcium chromate, had resulted in a distinct reduction in bronchial carcinoma mortality among workers exposed for the first time after the change-over (completed in 1958 in Leverkusen and 1964 in Uerdingen). A total of 1417 workers with at least 1 year of exposure were enrolled in the study. The observation period ended on 31 December 1988. The expected number of deaths was calculated using population statistics for North Rhine-Westphalia. The risk was determined in the form of a standardised mortality ratio (SMR), i.e. the ratio of observed deaths to expected deaths. In the group of 739 workers exposed before the process change-over was completed, 432 died during the observation period, 66 of them from bronchial carcinoma. This significant excess produced an SMR of 2.27 (95% confidence interval: 1.78-2.85). Where the cause of death was unknown, cases were allocated to a cause of death on the basis of the percentage occurrence of various causes of death in the specific subcohort. The cohort of 678 workers first exposed after the process modification had been completed had a slightly increased SMR for lung cancer of 1.26 (95% confidence interval: 0.58-2.38) based on nine cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemical detection of pulmonary cytochrome P450IA and metabolic activities associated with P450IA1 and P450IA2 isozymes in lung cancer patients.

The main polycyclic aromatic hydrocarbon-inducible cytochrome P450 was studied in lung tissue from 57 lung cancer patients by immunohistochemistry, using a monoclonal antibody (1-7-1) that recognizes P450IA1 and P450IA2 isozymes. The intensity of immunostaining was compared with the pulmonary activity of a P450IA1-dependent enzyme, aryl hydrocarbon hydroxylase (AHH), and with P450IA2-related metabolic activity estimated from the ratio of caffeine metabolites in urine. Immunostaining was not observed in peripheral lung tissue of nonsmokers or ex-smokers but was seen in the bronchiolar and alveolar epithelium of all patients who were smokers and had a peripheral carcinoma (16/16) and of 60% (10/17) of those who had a bronchial carcinoma. AHH activity was positively related to the intensity of immunostaining, and an almost 2-fold increase due to smoking was detected in the ratios of caffeine metabolites. These results demonstrate that tobacco smoke induces P450IA1 in the lung and probably P450IA2 in the liver, and suggest a role for certain metabolic phenotypes of P450IA1 in peripheral pulmonary carcinoma.

Variable regression of experimental bronchial preneoplasia during carcinogenesis.

It has been thought that squamous severe atypical metaplasia of the bronchus is reliably precancerous. The canine subcutaneous bronchial autograft model for studying the progression of epidermoid carcinogenesis (normal----regular squamous metaplasia----mild, moderate, and severe atypical metaplasia----squamous cell carcinoma) provides evidence that severe atypical metaplasia of the bronchial epithelium is reversible. Among 148 subcutaneous bronchial autografts that had serial sampling of the epithelium and exposure to implants of methylcholanthrene, severe atypical metaplasia was noted in 28 that received only a single implant. During the total carcinogen exposure (median 24.5 months), 9 of 28 (32%) developed squamous cell cancer, and 19 of 28 (68%) regressed toward normal. Severe atypical metaplasia was noted in 34 subcutaneous bronchial autografts that received two or more carcinogen implants: epidermoid cancer developed in 26 of 34 (76.5%), and regression toward or to normal occurred in 8 of 34 (23.5%). Severe atypical metaplasia was not detected in 53 subcutaneous bronchial autografts: 19 that received only a single implant and 34 that received two or more implants. Progression and regression occurred among these subcutaneous bronchial autografts in proportions similar to those found in subcutaneous bronchial autografts wherein severe atypical metaplasia was seen. Among 33 subcutaneous bronchial autografts initially studied after 6 months of exposure to carcinogen, progression to severe atypical metaplasia was seen 3 months later in 19 of 33 that had additional exposure; in the same interval regression of epithelial abnormalities occurred in 14 of 33 subcutaneous bronchial autografts that had no additional exposure (p less than 0.05). We have presented evidence that severe atypical metaplasia includes at least three cell populations: one committed to cancer without further stimulus, one that regresses despite further carcinogen exposure, and one that requires additional carcinogen to progress to cancer. At least in this model, severe atypical metaplasia is not inexorably precancerous. The subcutaneous bronchial autograft model is suitable for seeking biologic indicators of irreversibility.

[Familial clustering of asbestos-related diseases]. / Familiaer opphopning av asbestrelatert sykdom.

This article describes the case histories of four individuals in the same family, all of whom developed asbestos-related disease. Special emphasis is placed upon the case of a woman, who after seemingly minimal exposure to asbestos, in the form of cleaning her husband's working clothes, developed a malignant mesothelioma. The incidence of asbestos-related disease has increased steadily over the past ten years. This probably reflects the extensive use of asbestos in Norway since World War II, and the long latency period of the disease. The authors recommend obtaining an in-depth history of exposure when asbestos-related disease is suspected.

[Asbestos-induced lung diseases]. / Asbestfremkaldte lungesygdomme.

Asbestos fibres have potent cancerogenic and fibrogenic properties and may lead to development of cancer and fibrosis in the lung parenchyma and pleura. The Danish Ministry of Employment has established rules which should prevent development of disease when working with asbestos in future but, on account of the very long latent period between exposure and development of asbestos-related disease, these conditions will still occur during the next 30-40 years. Primarily, the more benign pleural plaques will be concerned but serious disease such as bronchial carcinoma and pleural mesothelioma will occur in the future. When patients are encountered who present symptoms or objective/paraclinical findings which are compatible with disease produced by asbestos, it is important to remember that exposure to asbestos may be many decades ago and, particularly where the malignant conditions are concerned, exposure need not have been particularly massive or prolonged. All cases where asbestos-related disease is suspected should be notified to the insurance administration.

Cancer after exposure to metronidazole.

We assessed the risk of occurrence of cancer associated with exposure to metronidazole in the 771 female residents of Rochester, Minnesota, who were treated with metronidazole for vaginal trichomoniasis during the period 1960 through 1969 and were followed up for a total of 12,628 person-years. Standardized morbidity and mortality ratios were determined by using an expected number calculated by applying age-specific incidence rates from Rochester studies and Cancer Surveillance, Epidemiology, and End-Results Reporting (SEER) data to the person-years of follow-up. The overall standardized morbidity ratios for cancer at all sites were 1.4 (Rochester, 1978 through 1983), 1.5 (SEER data for Iowa, 1978 through 1981), and 1.2 (SEER data for Connecticut, 1978 through 1981). By site of the cancers, the standardized morbidity ratios greater than unity were those for malignant lesions of the lung, breast, thyroid, bladder, brain, kidney, nasopharynx, and oral cavity, as well as for multiple myeloma and malignant melanoma; however, the only significantly elevated standardized morbidity ratio was that for bronchogenic carcinoma. After adjustment for smoking status, the standardized morbidity ratio for bronchogenic cancer was 2.5 (95% confidence interval of 1.3 to 4.4). The standardized mortality ratio for cancer at all sites was 1.4 (95% confidence interval of 0.9 to 2.2). The analysis of these data suggests no significant increase in cancer-related morbidity or mortality for women exposed to metronidazole for treatment of vaginal trichomoniasis.