linoleic-acid and Carcinoma--Squamous-Cell

Oral squamous cell carcinoma (OSCC) is a remarkable health problem worldwide, but its pathogenesis remains unknown. The aim of this study was to compare fat composition and secretory phospholipase-A2 (sPLA2) activity between the malignant and adjacent normal squamous tissues in patients with OSCC.. Paired samples of malignant squamous and adjacent normal-appearing tissues were collected from 27 patients with OSCC. The fatty acid composition in the obtained tissues was determined by gas liquid chromatography. Tissue enzyme activities of sPLA2 were measured using the standard assay with Diheptanoyl Thio-Phosphatidylcholine as substrate.. In the OSCC tissue, the level of stearic acid (18:0) and activity of sPLA2 were higher (P < 0.001), and the levels of oleic acid (18:1n-9) and linoleic acid (18:2n-6) were lower than that in the adjacent normal-appearing squamous tissue (P < 0.001). The activity of sPLA2 in OSCC was strongly negatively correlated with the amount of 18:2n-6 (r = -0.41, P < 0.001). Negative significant associations were observed between the OSCC invasion and tissue levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHE).. The changes in the fatty acid composition and sPLA2 activity may be regarded as indicators of altered lipid metabolism occurring in vivo during squamous cell carcinogenesis.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Female; Humans; Linoleic Acid; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness; Oleic Acid; Oropharyngeal Neoplasms; Phospholipases A2; Stearic Acids

The incidence of squamous cancer of the esophagus varies up to a hundredfold in different regions of the world. In Transkei, South Africa, a particularly high incidence of the disease is observed. We have previously proposed an association between a maize-rich diet and elevated levels of intragastric prostaglandin E2 production (PGE(2)). Here we investigate the molecular mechanisms by which a high-maize diet could lead to increased incidence of squamous cancer of the esophagus. We confirm that levels of PGE(2) are high (606.8 pg/ml) in the gastric fluid of individuals from Transkei. We also show that treatment of esophageal cells with linoleic acid, which is found at high levels in maize and is a precursor to PGE(2), leads to increased cell proliferation. Similarly, treatment of cells with PGE(2) or with gastric fluid from Transkeians also leads to increased proliferation. Our data suggest that the high levels of PGE(2) associated with a maize-rich diet stimulate cell division and induce the enzyme COX 2, resulting in a positive feedback mechanism that predisposes the esophagus to carcinoma.

Topics: Black People; Carcinoma, Squamous Cell; Cell Line; Cell Proliferation; Cyclooxygenase 2; Diet; Dinoprostone; Disease Susceptibility; Esophageal Neoplasms; Esophagus; Feedback, Physiological; Gastric Juice; Gene Expression Regulation, Neoplastic; Humans; Linoleic Acid; Risk Factors; RNA, Messenger; Seeds; South Africa; Surveys and Questionnaires; Zea mays

Tumor promotion potential of diacylglycerol (DAG)-rich edible oil was examined using a two-stage mouse skin carcinogenesis model initiated with 7,12-dimethylbenz[a]anthracene (DMBA). Topical treatment with 75 mg DAG oil once a day for 5 days/week for 35 weeks caused papillomas in 4 of 23 (17%) DMBA-treated female ICR mice, while DMBA initiation alone and DAG treatment without DMBA initiation did not induce any skin tumors. Doubling the daily treatment (twice a day x 5 days/week) at doses of 75 and 30 mg caused both papillomas and squamous cell carcinomas after DMBA initiation, the incidences of tumors being 48% (12/25) and 44% (11/25), respectively, significantly higher than the 4% (1/23) in the DMBA+ 85 mg triacylglycerol group and 0% (0/24) in the DMBA+ vehicle-treated group. The results indicate that DAG-rich oil has promoting potential for skin carcinogenesis, and thus, further investigations of its tumor-promoting potential in other organs are warranted.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Diglycerides; Fatty Acids; Female; Fluocinolone Acetonide; Linoleic Acid; Mice; Oils; Oleic Acid; Protein Kinase C; Skin Neoplasms; Tetradecanoylphorbol Acetate

Endemic cancer of the oesophagus in Africa is associated with the use of maize as the staple. In one African community endemic cancer of the oesophagus has been shown to have a strong statistical association with the consumption of foods based on maize in the meal form. A strong association with consumption of maize meal has also been shown in a region of Italy. It has been argued in the past that the association with maize consumption is due to a fortuitous association; or due to the nutritional deficiencies of maize meal; or due to fungal contamination. We argue that maize meal is a distinctly different food from whole maize, and that nutritional content as much as deficiency is responsible for predisposition of the oesophagus to carcinogenesis. An important factor is the breakdown of esterified linoleic acid to the free form in stored maize meal. This leads to excess production of prostaglandin E2 in the stomach. The excess Prostaglandin E2 causes a low-acid duodenogastro-oesophageal reflux, which predisposes to carcinogenesis. Supporting evidence is available that the steps of this mechanism occur in endemic areas, and that they are associated with the carcinogenic process. Health measures including poverty alleviation, health education, and monitoring and control of maize meal storage and content may be required to reduce the incidence of this disease in Africa.

Topics: Africa; Carcinoma, Squamous Cell; Corn Oil; Diet; Dinoprostone; Disease Susceptibility; Endemic Diseases; Esophageal Neoplasms; Fatty Acids, Nonesterified; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Incidence; Linoleic Acid; Models, Biological; Zea mays

In 1996-2004 a case-control study on nutrient intake, dietary constituents and risk of squamous cell carcinoma of the esophagus was conducted in Montevideo, Uruguay. In fact, Uruguay, and especially its northern provinces, which border Brazil, are high-risk areas. The study included 234 cases and 936 controls. The controls were hospitalized patients with non-neoplastic disease, which was not related to tobacco smoking and alcohol drinking, and without recent changes in their diets. Controls were frequency matched to cases on age (10-yr intervals), sex, and residence (Montevideo and other provinces). Dietary constituents were energy adjusted using the residuals method and then categorized in quartiles according to the distribution of the controls. The final model included linoleic acid, lycopene, alpha-carotene, beta-cryptoxanthin, vitamin A, monounsaturated fat, total carbohydrates, beta-carotene, and folate. The odds ratio (OR) for high intake of linoleic acid was 1.4 (95% confidence interval, CI = 1.2-1.6), whereas lycopene displayed a strong protective effect (OR = 0.7; 95% CI = 0.6-0.9). The possible role of these and other dietary constituents in esophageal carcinogenesis is discussed.

Topics: Adult; Aged; Aged, 80 and over; Anticarcinogenic Agents; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Confidence Intervals; Diet; Diet Surveys; Esophageal Neoplasms; Female; Humans; Linoleic Acid; Lycopene; Male; Middle Aged; Odds Ratio; Risk Factors; Uruguay; Vitamins

An in vitro study was conducted to determine if malignant transformation can be induced in human urothelial cells immortalized with human papillomavirus E6/E7 genes. A clone designated 1T1 was isolated and then stably transfected with an acyl CoA oxidase (ACOX)-expression construct. The cells generated H2O2 in a large quantity from the substrate linoleic acid (LA). After 56 days of LA treatment, cells persistently formed an epithelial cyst in athymic nude mice with an occasional intracystic epithelial nodule. Our results indicate that human urothelial cells can be transformed to low grade neoplastic cells by H2O2 and suggest that H2O2 may be involved in the development of bladder cancer.

Topics: Acyl-CoA Oxidase; Aged; Animals; Blotting, Northern; Blotting, Western; Carcinoma, Squamous Cell; Cell Division; Cell Transformation, Neoplastic; Cells, Cultured; Humans; Hydrogen Peroxide; Karyotyping; Linoleic Acid; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Oxidoreductases; Peroxisomes; Rats; Transfection; Urothelium

Topics: Adult; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Cycle; Cell Division; Humans; Linoleic Acid; Mitosis; Neoplasm Invasiveness; Predictive Value of Tests; Sensitivity and Specificity; Skin Neoplasms

In order to investigate the possible mechanisms underlying platelet functional changes in patients affected by neoplasms, platelet lipid composition, plasma beta-thromboglobulin (Beta-TG) and serum thromboxane B2 (TXB2) were investigated in 16 male patients affected by pulmonary carcinoma and in 16 comparable control subjects. In patients high levels of plasma Beta-TG (67 +/- 9 versus controls 14 +/- 4 ng/ml, p < 0.001) and serum TXB2 (434 +/- 56 versus 223 +/- 48 ng/ml, p < 0.001) were observed. Also platelet lipid composition was found altered in patients with respect to controls (lower percent levels in n-3 fatty acids and in linoleic acid esterified in the main platelet phospholipid fractions: at least p < 0.05). These results indicate that in vivo platelet activation is detectable in neoplastic patients and it is associated with alterations in platelet lipid composition. In the light of the important role played by membrane lipids in platelet functions related to thrombosis and haemostasis we conclude that platelet lipid changes could cooperate in platelet activation and increased thrombotic risk so frequently observed in neoplastic disease.

Topics: Adult; beta-Thromboglobulin; Blood Platelets; Carcinoma, Squamous Cell; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Linoleic Acid; Linoleic Acids; Lipids; Lung Neoplasms; Male; Platelet Activation; Platelet Factor 4; Thromboxane B2

Little is known about the aetiology of Barrett's oesophagus, a condition in which columnar epithelium replaces normal squamous epithelium above the juncture of the oesophagus with the stomach. An exploratory retrospective study of males from the Tucson Veteran's Affairs Medical Center (Tucson, AZ, USA), looking at 22 Barrett's cases and 22 controls, was undertaken to: (1) determine whether risk factors previously reported for squamous oesophageal cancer were also potential risk factors for Barrett's oesophagus; and (2) explore which of several retrospectively determined dietary factors would permit maximum discrimination of Barrett's cases from controls. Because of the recognized difficulty with retrospective dietary assessment, an intensive interview-based life history approach was developed to assess behavioural factors throughout adulthood. We examined the dose-response relationship involving questions (1) and (2) separately for subjects with lesions less than or greater than 7 cm in length. A literature-based oesophageal cancer risk factor score (including use of tobacco and intakes of alcohol, fat, vitamin A, linoleic acid and protein) discriminated cases from controls. Alcohol consumption alone discriminated patients with lesions < 7 cm in length from controls, and a more complex risk factor score (including tobacco use, alcohol, fat, fruits and vegetables) discriminated patients with lesions > 7 cm in length from controls.

Topics: Adult; Aged; Alcohol Drinking; Barrett Esophagus; Carcinoma, Squamous Cell; Case-Control Studies; Dietary Fats; Dietary Proteins; Esophageal Neoplasms; Feeding Behavior; Fruit; Health Behavior; Humans; Interviews as Topic; Life Style; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors; Smoking; Vegetables; Vitamin A