Squalene, olive oil, and cancer risk: a review and hypothesis

Epidemiological studies of breast and pancreatic cancer in several Mediterranean populations have demonstrated that increased dietary intake of olive oil is associated with a small decreased risk or no increased risk of cancer, despite a higher proportion of overall lipid intake. Experimental animal model studies of high dietary fat and cancer also indicate that olive oil has either no effect or a protective effect on the prevention of a variety of chemically induced tumors. As a working hypothesis, it is proposed that the high squalene content of olive oil, as compared to other human foods, is a major factor in the cancer risk-reducing effect of olive oil. Experiments in vitro and in animal models suggest a tumor-inhibiting role for squalene. A mechanism is proposed for the tumor-inhibitory activity of squalene based on its known strong inhibitory activity of beta-hydroxy-beta-methylglutaryl-CoA reductase catalytic activity in vivo, thus reducing farnesyl pyrophosphate availability for prenylation of the ras oncogene, which relocates this oncogene to cell membranes and is required for the signal-transducing function of ras.     

Thyroid cancer: a review

Thyroid cancer is a rare and complex disease. The thyroid contains various cell types from which distinct diseases arise. These malignancies range from indolent to extremely aggressive. Diagnosis includes attention to risk factors, family history, and subjective reports. The most valuable tool for diagnosis is the fine-needle aspiration. Primary treatment is surgery with postoperative hormone therapy. Radiation and chemotherapy serve palliative and adjuvant roles in advanced, recurrent, or metastatic disease. Nurses make a significant contribution to patient understanding and successful treatment outcome.     

Estrogen use and cancer risk: a review

The role of estrogens as carcinogens, cocarcinogens or tumor promoters, as well as their mechanism(s) of action on cancer cells, are thoroughly reviewed. Although there is ample evidence that estrogens (natural and synthetic) can induce multiple benign and malignant tumors in animals, and most of these tumors are histologically similar to that in humans, there is no direct evidence that natural estrogens (estradiol-17 beta, estrone) are carcinogenic in humans. Recent evidence in cellular and molecular oncology revealed that estrogens act by genetic and epigenetic mechanisms on cancer cells, and a close relationship between estrogens, growth factors, and oncogenes is important for human cancer. Long-term exposure to estrogens should always be regarded as increased cancer risk. Estrogen replacement therapy (ERT) by unopposed estrogens in postmenopausal women with high familial cancer risk or existent premalignant lesions should be avoided, since estrogens may act as tumor promoters. Combination of estrogens with progesterone (or other progestins) cyclically or sequentially, significantly reduce and prevent the cancer risk.     

Breast cancer associated mucin: a review

Rabbit polyclonal antibody against mouse EHS laminin was used to investigate the distribution and composition of laminin in the rat first molar tooth germ. Immunohistochemical analysis showed that laminin is expressed in the inner and outer epithelia of the enamel organ and in small blood vessels in the dental papilla and strellate reticulum. Immunoblots revealed that tooth germ laminin differs from EHS laminin. Tooth germ laminin contains beta chains, while the alpha 1 chain is substituted by a 300-kDa chain. Two-dimensional electrophoresis analysis of tooth germ extract showed that beta chains appeared as four spots with approximate pI values of 6.6, 7.5, 7.8 and 8.5. These results indicate that more than-one type of laminin isoform is present in the first molar tooth germ. Additionally, we have shown that despite the early degradation of tooth germ basement membrane, the laminin molecule is still intact at the time of birth.     

Potassium and sodium intake and excretion in calcium stone forming patients

We reviewed the results of 15 patients (16 feet) in whom a hallux valgus procedure had failed. Salvage was by proximal crescentic first metatarsal osteotomy with distal soft-tissue reconstruction. Results based on a clinical scale considering the level of pain, activity limitations, support requirement, footwear limitations, and alignment were good in 11, fair in two, and poor in three. Patients were satisfied with the results in 10 feet, satisfied with reservations in four feet, and dissatisfied in two feet. Complications were: transfer metatarsalgia in three, hallux varus in one, and osteotomy nonunion in one. One of the patients required reoperation to bone graft a proximal osteotomy. Metatarsal osteotomy was helpful in the salvage treatment of recurrent, symptomatic hallux valgus when the first metatarsophalangeal joint was functional and painless.     

Economic issues in lung cancer: a review

PURPOSE: Lung cancer is a major source of morbidity, mortality, and health care costs in the developed and developing world. It is estimated that lung cancer is responsible for 20% of all cancer care costs. Concerns exist that this expenditure is associated with questionable benefits. DESIGN: The economic literature that relates to smoking was reviewed, followed by a summary of the economics of the diagnosis, treatment, and palliation of lung cancer. Methodologic considerations are also discussed in this section. RESULTS: Published studies suggest that the increased lifetime health care costs from smoking-related illnesses in smokers are partially or fully offset by the higher medical costs that result from increased longevity in nonsmokers. However, lost productivity costs, which result from morbidity and early mortality among smokers, result in an overall net cost of smoking to society. Discounting rates of 3% to 5% do not substantively alter these results. The per-patient cost to treat lung cancer is substantial. The major cost center is hospitalization; palliative or terminal treatment is associated with significant costs. Savings can be obtained through the judicious use of diagnostic and staging procedures. Furthermore, combined modality treatment approaches and the palliative use of combination chemotherapy appear to be associated with acceptable cost-effectiveness compared with commonly used therapies for other diseases. CONCLUSION: Although the increased medical care costs of treating smoking-related diseases are somewhat offset by the higher medical care costs due to increased longevity in nonsmokers, the lost productivity that results from smoking results in a net cost to society. Standard approaches to the management of lung cancer are associated with cost-effectiveness similar to that of other commonly used medical interventions.     

Targeting gene therapy to cancer: a review

In recent years the idea of using gene therapy as a modality in the treatment of diseases other than genetically inherited, monogenic disorders has taken root. This is particularly obvious in the field of oncology where currently more than 100 clinical trials have been approved worldwide. This report will summarize some of the exciting progress that has recently been made with respect to both targeting the delivery of potentially therapeutic genes to tumor sites and regulating their expression within the tumor microenvironment. In order to specifically target malignant cells while at the same time sparing normal tissue, cancer gene therapy will need to combine highly selective gene delivery with highly specific gene expression, specific gene product activity, and, possibly, specific drug activation. Although the efficient delivery of DNA to tumor sites remains a formidable task, progress has been made in recent years using both viral (retrovirus, adenovirus, adeno-associated virus) and nonviral (liposomes, gene gun, injection) methods. In this report emphasis will be placed on targeted rather than high-efficiency delivery, although those would need to be combined in the future for effective therapy. To date delivery has been targeted to tumor-specific and tissue-specific antigens, such as epithelial growth factor receptor, c-kit receptor, and folate receptor, and these will be described in some detail. To increase specificity and safety of gene therapy further, the expression of the therapeutic gene needs to be tightly controlled within the target tissue. Targeted gene expression has been analyzed using tissue-specific promoters (breast-, prostate-, and melanoma-specific promoters) and disease-specific promoters (carcinoembryonic antigen, HER-2/neu, Myc-Max response elements, DF3/MUC). Alternatively, expression could be regulated externally with the use of radiation-induced promoters or tetracycline-responsive elements. Another novel possibility that will be discussed is the regulation of therapeutic gene products by tumor-specific gene splicing. Gene expression could also be targeted at conditions specific to the tumor microenvironment, such as glucose deprivation and hypoxia. We have concentrated on hypoxia-targeted gene expression and this report will discuss our progress in detail. Chronic hypoxia occurs in tissue that is more than 100-200 microns away from a functional blood supply. In solid tumors hypoxia is widespread both because cancer cells are more prolific than the invading endothelial cells that make up the blood vessels and because the newly formed blood supply is disorganized. Measurements of oxygen partial pressure in patients' tumors showed a high percentage of severe hypoxia readings (less than 2.5 mmHg), readings not seen in normal tissue. This is a major problem in the treatment of cancer, because hypoxic cells are resistant to radiotherapy and often to chemotherapy. However, severe hypoxia is also a physiological condition specific to tumors, which makes it a potentially exploitable target. We have utilized hypoxia response elements (HRE) derived from the oxygen-regulated phosphoglycerate kinase gene to control gene expression in human tumor cells in vitro and in experimental tumors. The list of genes that have been considered for use in the treatment of cancer is extensive. It includes cytokines and costimulatory cell surface molecules intended to induce an effective systemic immune response against tumor antigens that would not otherwise develop. Other inventive strategies include the use of internally expressed antibodies to target oncogenic proteins (intrabodies) and the use of antisense technology (antisense oligonucleotides, antigenes, and ribozymes). This report will concentrate more on novel genes encoding prodrug activating enzymes, so-called suicide genes (Herpes simplex virus thymidine kinase, Escherichia coli nitroreductase, E. (ABSTRACT TRUNCATED)     

Scintigraphic imaging of breast cancer: a review

Scintimammography is a recently verified technique that will expand the use of nuclear medicine to a new group of patients in whom scintigraphic imaging has not been widely used. If performed correctly, and in certain groups of patients, it delivers a sensitivity as high as X-ray mammography or magnetic resonance imaging (MRI) in palpable tumours but with greater specificity. It is best used in patients in whom X-ray mammography, ultrasound and MRI prove non-diagnostic or unhelpful, particularly those women with dense breasts or who have had previous breast surgery. The mechanism of uptake of 99Tcm-MIBI in breast tissue is only partly understood and in itself may help in determining important aspects of tumour function, such as the response to cytotoxic chemotherapy. Other scintigraphic methods for imaging breast cancer may be able to look at other aspects of cancer function, for example blood supply, metabolic rate or the in vivo assessment of oestrogen or somatostatin receptor status. This in turn may be useful in planning treatment. Metastatic disease may best be monitored with 18F-FDG PET, which has a sensitivity greater than MRI but a similar specificity. Much furtner work will need to be done on the use of nuclear medicine in breast cancer, but the addition of unique functional information to the anatomical data from X-ray and MRI should benefit future patients' management.     

Surviving cancer: a review of the impact and consequences

In this critical review of the literature, the author examines articles assessing the effects on patients of cancer survival. Implications for nursing practice, education and research are also discussed.     

Chemotherapy in non-small cell lung cancer: a review

Lung cancer, of which non-small cell carcinoma is the most common, has been a significant therapeutic challenge for decades and will remain so for decades to come. Despite its prevalence, progress in the management of non-small cell lung cancer has been relatively slow. This is in part due to the pessimism of most physicians treating this disease, which has resulted in a relatively lackadaisical attitude with regards to clinical trials when compared to other solid tumours like breast or colorectal cancers. Nevertheless, the past decade has seen significant progress, specifically with regards to the management of locally advanced disease. Chemotherapy, though shown to be biologically active in non-small cell lung cancer, is considered an ineffective palliative tool in the setting of metastatic disease due to its toxicities and the "less than encouraging" response rates generated by the cisplatin-based combination regimen which is generally considered to be the most active currently available. The advent of new active agents such as paclitaxel and vinorelbine which are potentially less toxic may change this view. Conversely, the response rate of locally advanced disease to chemotherapy is significantly higher and this has resulted in numerous multimodality trials of neoadjuvant chemotherapy prior to surgery and/or radiation. To date, a number of randomised trials have shown that this approach can result in significant survival benefit for patients with locally advanced disease. An alternative approach makes use of the potential synergism between certain chemotherapeutic agents (such as cisplatin) and radiation when used concurrently. However, data on concurrent chemoradiotherapy in locally advanced disease have been largely based on single-arm studies and are inconclusive. Three randomised trials on concurrent chemoradiotherapy have been shown benefit for the use of combined modality in locally advanced disease. Hence, treatment of locally advanced disease should include chemotherapy as part of the combined modality approach. However, the optimal sequencing of these modalities would require well-designed randomised trials to determine.     

Telomerase: a promising marker of biological immortality of germ, stem, and cancer cells. A review

This review will describe the current state of knowledge of telomerase as it relates to human malignancies, focusing primarily on published measurements of this enzymes activity in benign and malignant neoplasms and their normal tissue counterparts. Key questions concerning the potential clinical utility of assaying for telomerase activity will be addressed and the implications of recent findings discussed.     

Fatigue in cancer patients: a review of the literature

This paper reviews the research literature concerning fatigue in cancer patients, evaluating the quality of the evidence, thus helping to focus the direction and methodological rigour required in future investigations. Since fatigue in this population has been attributed to several mechanisms these will be discussed. The prevalence of fatigue in cancer patients will then be documented. An overview of what is currently understood about fatigue in cancer will follow. Based on the literature, conceptual and methodological difficulties will be described. Finally, gaps in understanding will be identified. Suggestions for future research will be formulated and potential interventions to decrease feelings of fatigue explored.     

Primary fallopian tube cancer: a review of the literature

BACKGROUND: We conducted a population-based case-control study to describe the relationship between occupational exposure to estrogenic chemicals and the occurrence of breast cancer in Cape Cod, Massachusetts. METHODS: Incident cases of breast cancer (n = 261) diagnosed from 1983 through 1986 and controls (n = 753) were interviewed to gather information on breast cancer risk factors and all full-time jobs held since age 18. Blinded exposure assessments were employed using the data from the NIOSH National Occupational Exposure Survey, chemical production and usage information, and the expert judgement of a certified industrial hygienist. RESULTS: Overall, 29.5% of cases and 32.5% of controls had probable occupational exposure to one or more xenoestrogens. Probable exposure to nonylphenol (21.5% of cases, 21.4% of controls), butyl benzyl phthalate (10.0% of cases, 13.2% of controls), BHA (7.3% of cases, 9.6% of controls), bisphenol A (9.6% of cases, 11.6% of controls), and 4-tert-butylphenol (2.7% of cases and 5.3% of controls) were relatively commons, while probable exposure to the other xenestrogens was rare. Only PCBs and 4-octylphenol were associated with moderate increase in the odds of breast cancer (PCBs: 5 exposed cases and 6 exposed controls, adjust odds ratio: 3.2, 95% CI = 0.8-12.2, and 4-octylphenol: 6 exposed cases and 5 exposed controls, adjusted odds ratio: 2.9, 95% CI = 10.8).     

Hepatitis, HIV, and the dermatologist: a risk review

The practice of dermatology has always carried with it the risk of patient-acquired infection. This review covers health risks associated with the care of HIV-infected patients and patients who are chronic carriers of hepatitis B or C virus, protection options to reduce exposure, and protocols should exposure occur. Hepatitis B continues to be a major risk to health care workers, killing approximately 200 per year. In contrast, as of 1990, only 327 total health care personnel had acquired HIV, with no deaths reported. Data are lacking regarding hepatitis C, but it appears to be an increasing concern. Needlesticks are the most common form of occupational transmission, with an infectivity rate of 30% for hepatitis B, 3% for hepatitis C, and 0.3% for HIV. Universal precautions are the cornerstones of safety. Hepatitis B vaccination, zidovudine prophylaxis, and hepatitis C therapy are discussed as postexposure recommendations are reviewed.     

Genetic, cytogenetic, and carcinogenic effects of radon: a review

Radon exposure has been linked to lung carcinogenesis in both human and animal studies. Studies of smoking and nonsmoking uranium miners indicate that radon alone is a risk factor for lung cancer at the levels encountered by these miners, although the possibility exists that other substances in the mine environment affect the radon-induced response. The relevance of data from mines to the lower-exposure home environment is often questioned; still, a recent study of miners exposed to relatively low radon concentrations demonstrated a statistically significant increase for lung and laryngeal cancer deaths. In two major series of experiments with rats, the primary carcinogenic effect found was respiratory tract tumors, and evidence for an inverse exposure-rate effect was also noted. Although this inverse dose-rate effect also has been described in underground miner studies, it may not similarly apply to radon in the home environment. This observation is due to the fact that, below a certain exposure, cells are hit once or not at all, and one would not expect any dose-rate effect, either normal or inverse. Because some chromosome aberrations persist in cycling cells as stable events, cytogenetic studies with radon are being performed to help complete the understanding of the events leading to radon-induced neoplasia. Radon has been found to induce 13 times as much cytogenetic damage (as measured by the occurrence of micronuclei) than a similar dose of 60Co. A wide variety of mutation systems have demonstrated alpha-particle mutagenesis; recent investigations have focused on the molecular basis of alpha-induced mutagenesis. Gene mutations are induced by radon in a linear and dose-dependent fashion, and with a high biological effect relative to low-LET irradiation. Studies of the hprt locus show that approximately half of the alpha-induced mutations arise by complete deletion of the gene; the remaining mutations are split between partial deletions, rearrangements, and events not detectable by Southern blot or PCR exon analysis. Although other mutation systems do not show the same spectra as observed in the hprt gene (suggesting that the gene environment affects response), DNA deletions or multilocus lesions of various size appear to be predominant after radon exposure. As data emerge regarding radon-induced changes at the chromosomal and molecular level, the mechanisms involved in radon carcinogenesis are being clarified. This information should increase the understanding of risk at the low exposure levels typically found in the home.     

Nonstandard fractionation schedules in radiation therapy of head and neck cancer: a review

The authors present an updated review of the clinical trials on hyperfractionated and accelerated fractionation schedules in radiotherapy of head and neck cancer. The available results in terms of survival and local control, and acute and late toxicity data are summarized in order to show the current status of this research field. The new breed of fractionation schedules that are on study, designed on the ground of new rationales, are presented as well. Finally, an introductory overview of combination therapy including non standard fractionation radiotherapy associated with chemotherapy is reported.     

Risk, motives, and styles of utilization review: a cross-condition comparison

In the United States various forms of managed care have been introduced to control the use of expensive medical services. One of the most prominent involves utilization review of hospital admissions. While reviewing the appropriateness of inpatient treatment is appealing in principle, its application is made difficult by clinical uncertainty. Managed care plans develop and implement review criteria often without the guidance of clear clinical norms of treatment. Under these conditions, we suggest that utilization review organizations (UROs) can be expected to develop "styles" of review that respond to clinical uncertainty, influenced by their experience, professional orientation, and financial incentives. Two review styles are explored in this paper: standardization, where the URO reduces the variance in clinical practices by eliminating those practices that deviate from professional norms and stringency, whereby the URO shifts the distribution of clinical practice as it tries to change the professional norms of practice. Data from a 1992-1993 national survey of utilization review organizations are used to test whether UROs have review styles that systematically respond to organizational attributes, economic pressures, and clinical uncertainty associated with three medical conditions: cardiac catheterization, low back pain, and adolescent depression. UROs were found to adopt more stringent review strategies for conditions with weaker norms of appropriate treatment. Financial incentives and organizational experience are positively related to greater stringency. Standardization responds to professional orientation and organizational experience. Variation in the review styles of UROs has implications for the resulting distribution of clinical practices as well as the equity of access to medical care.