Intake of Freshwater Fish and Associated Fatty Acids and Risk of Breast Cancer

To investigate the association between intake of freshwater fish and their fatty acids and the risk of breastcancer in Chinese women, we conducted a case-control study with 669 cases and 682 population-based controlsin Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. Unconditionallogistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Totalfreshwater fish intake was linked to decrease in the adjusted OR for breast cancer, but without dose-dependence.Analyses by freshwater fish species showed that consumption of black carp and silver carp was inversely relatedto breast cancer risk, with adjusted-ORs for the highest intake category of black carp (≥500g/month) of 0.54(95%CI=0.33-0.92; P trend<0.002) and for silver carp (≥1000g/month) of 0.19 (95%CI=0.11-0.33; P trend<0.001).In contrast, consumption of crucian carp was positively related to breast cancer risk, with an adjusted OR forthe highest intake category (≥1000g/month) of 6.09 (95%CI=3.04-12.2; P trend<0.001). Moderate intakes of SFA,PUFA, n3-PUFA and n6-PUFA from freshwater fish may decrease the risk of breast cancer among premenopausalwomen. The findings of this study suggest that intake of freshwater fish and their fatty acids may modify risk ofbreast cancer, and that different species of freshwater fish could have a different actions on breast cancer risk.Future epidemiologic studies are needed to know the effects of freshwater fish intake on breast cancer risk andthe cause of these effects.     

Protective Effect of Omega-3 Fatty Acids in Fish Consumption Against Breast Cancer in Asian Patients: A Meta-Analysis

Objective: This systematic review and meta-analysis was performed to determine the protective effect of omega-3fatty acids in fish consumption against breast cancer in Asian patients. Methods: The authors conducted a meta-analysisof published research articles on protective effect of omega-3 fatty acids in fish consumption against breast cancer inAsian patients published between January 2000 and July 2018 in online database of PubMed, ProQuest and EBSCO.Pooled odds ratios (OR) were calculated by using fixed and random-effect models. Publication bias was visuallyevaluated by using funnel plots and statistically assessed in Egger’s and Begg’s tests. Data were processed by ReviewManager 5.3 (RevMan 5.3) and Stata version 14.2 (Stata Corporation). Results: This study reviewed 913 articles.There were 11 studies which conducted systematic review then continued by meta-analysis of relevant data with totalnumber of samples were 130,365 patients. The results showed there was protective effect of omega-3 fatty acids in fishconsumption against breast cancer in Asian patients (OR = 0.80 [95% CI 0.73-0.87, p <0.00001]). There was not anystudy with significant publication bias included. Conclusion: This analysis confirmed the protective effect of omega-3fatty acids in fish consumption against breast cancer in Asian patients.     

Association of Dietary Intake Ratio of n-3/n-6 Polyunsaturated Fatty Acids with Breast Cancer Risk in Western and Asian Countries: A Meta-Analysis

Objective: This systematic review and meta-analysis were performed to determine association of dietary intake ratioof n-3/n-6 polyunsaturated fatty acids with breast cancer risk in Western and Asian countries. Methods: The authorsconducted a meta-analysis of published research articles on association of dietary intake ratio of n-3/n-6 polyunsaturatedfatty acids (PUFAs) with breast cancer risk in Western and Asian countries published between January 2000 and February2019 in online article databases of PubMed, ProQuest and EBSCO. Pooled risk ratios (RR) were calculated usingfixed and random-effect models. Publication bias was visually evaluated by performing funnel plots and statisticallyassessed by Egger’s and Begg’s tests. Data were processed by using Stata version 14.2 (Stata Corporation). Results:This study reviewed 913 articles. There were 13 studies included in systematic review continued by meta-analysisof relevant data with total number of samples: 275,264 patients. The results showed dietary intake ratio of n-3/n-6PUFAs with breast cancer risk in Western and Asian countries (RR = 0.99; 95% CI: 0.92-1.07). Dietary intake ratioof n-3/n-6 PUFAs with breast cancer risk in Western countries reached (RR = 0.98; 95% CI: 0.91-1.06) and there wasany significant publication bias for studies included. Dietary intake ratio of n-3/n-6 PUFAs with breast cancer risk inAsian countries reached (RR = 1.18; 95% CI: 0.94-1.47) and there was not any significant publication bias for studiesincluded. Conclusion: This analysis confirmed association of dietary intake ratio of n-3/n-6 PUFAs with breast cancerrisk in Western and Asian countries. Higher dietary intake ratio is associated with lower risk of breast cancer in Asiancountries rather than Western countries. This study suggests increasing dietary intake ratio n-3/n-6 PUFAs will providebenefit for breast cancer prevention.     

Organotropic Chemopreventive Effects of n-3 Unsaturated Fatty Acids in a Rat Multi-organ Carcinogenesis Model

Organotropic chemopreventive effects of n‐3 unsaturated fatty acids were studied using a multi‐organ carcinogenesis model in male rats. Rats were treated with diethylnitrosamine (DEN), N‐methyl‐N‐nitrosourea (MNU), N‐butyl‐N‐4‐hydroxybutylnitrosamine (BBN), 1,2‐dimethylhydrazine (DMH) and dihydroxy‐di‐n‐propylnitrosamine (DHPN) during the first 7 weeks, and then given unsaturated fatty acid (UFAs), docosahexaenoic acid (n‐3, C_22:6) (DHA), eicosapentaenoic acid (n‐3, C_20:5) (EPA), linoleic acid (n‐6, C_18:2) (LA) or oleic acid (n‐9, C_18:1) (OA) at a dose of 1.0 ml/rat, 3 tunes a week by gavage for the consecutive 30 weeks. All rats were fed a low LA basal diet throughout the experiment and a calorie‐restricted basal diet during the period of UFAs feeding administration. DHA significantly reduced tumor size and numbers in the large intestine as compared to OA treatment. Furthermore, DHA showed a tendency to inhibit carcinogenesis in the small intestine and lung. EPA also showed a tendency to inhibit intestinal carcinogenesis. On the other hand, LA showed a tendency to inhibit lung carcinogenesis, but to promote large intestinal carcinogenesis. However these UFAs did not influence preneoplastic and neoplastic lesion development in the liver, kidney, and urinary bladder. Levels of the administered fatty acids were clearly increased in the serum and organs. In contrast, arachidonic acid (AA) levels in the large and small intestines and liver were markedly decreased by treatment with DHA and EPA. Decreased levels of AA in the large intestine correlated well with tumor incidence, although the number of glutathione S‐transferase‐positive (GST‐P⁺) foci showed an inverse correlation with AA levels. The data thus provide evidence that an organotropism exists with regard to the influence of UFAs on carcinogenesis, which correlates with reduction of tissue AA levels in the target organs.     

不饱和脂酸及其硒化物对BEL-7402人肝癌细胞的杀伤作用及DNA合成的影响

研究了亚麻酸、亚油酸、油酸及其硒化物对人肝癌细胞杀伤作用及对ＤＮＡ合成的影响。结果表明，三种脂酸及其硒化物对ＢＥＬ－７４０２人肝癌细胞均有杀伤作用，其中以硒化亚麻酸杀伤作用最强，５００μｇ／ｍｌ即可杀灭全部肝癌细胞，且具剂量效应关系。其次是亚麻酸、亚油酸和硒化亚油酸。油酸和硒化油酸杀伤作用较弱。１５０μｇ／ｍｌ的亚麻酸、亚油酸及其硒化物和硒化油酸对肝癌细胞的ＤＮＡ合成均有明显抑制作用（Ｐ＜０．０１），其中以硒化亚麻酸抑制作用最强（Ｐ＜０．０５～０．０１），且具有剂量效应关系。亚麻酸、亚油酸对ＤＮＡ合成的抑制作用与相应的硒化物之间无明显差异（Ｐ＞０．０５），而只含一个双键的油酸对ＤＮＡ合成无明显抑制作用，其硒化物则有显著抑制作用，两者的差异非常显著（Ｐ＜０．０１）。     

Effect of free fatty acids on two-stage skin carcinogenesis in mice

The effect of n-3 and n-6 free fatty acids on two stage skin carcinogenesis in mice was studied. Stearic, linoleic, arachidonic, and eicosapentaenoic acids inhibited both initiation and promotion stages of skin carcinogenesis. Although no direct correlation between lipid peroxidation and papilloma formation was observed, a trend towards an increase in the formation of lipid peroxides with the inhibitory effect of fatty acids on papilloma development was noted. In general, the fatty acids applied were incorporated mainly into the phospholipid and free fatty acid pools. All the fatty acids tested, except eicosapentaenoic and docosahexaenoic acids, inhibited the binding of benzo[a]pyrene (BP) to DNA. On the other hand, BP and croton oil-induced skin cell proliferation was not influenced by any of the fatty acids used. In conclusion, the results of the present study suggest that inhibition of papilloma formation by free fatty acids is complex and can be attributed to a limited extent only to their ability to inhibit BP binding to DNA, to block cell proliferation and enhance the lipid peroxidation process.     

ω-3多不饱和脂肪酸对人胃癌BGC-823细胞PGE2、SOD和MDA的影响

目的：观察不同浓度ω-3多不饱和脂肪酸（EPA、DHA）对人胃癌BGC-823细胞存活情况、PGE2和脂质过氧化的影响。方法：采用MTF法测定肿瘤细胞存活率，酶联免疫吸附竞争法测定PGE2浓度，黄嘌呤氧化酶法测定总SOD活力，TBA法测定MDA含量。结果：30μg／ml和45μg／ml的EPA或DHA可显著降低肿瘤细胞存活率（P〈0．001），细胞PGE2浓度和总SOD活力明显下降（P〈0．05）、而MDA含量明显升高（P〈0．05）。结论：ω-3多不饱和脂肪酸可通过PGE2代谢和脂质过氧化作用抑制人胃癌BGC-823细胞的生长。     

Antitumor Activity of D-Mannosamine In Vitro: Cytotoxic Effect Produced by Mannosamine in Combination with Free Fatty Acids on Human Leukemia T-Cell Lines

Cytotoxic effects of mannosamine and free fatty acids on humanmalignant T-lymphoid cell lines derived from patients with T-cellleukemia were investigated. The combination of mannosamine andan unsaturated fatty acid (oleate or linoleate) produced morestriking cytotoxic effects on malignant lymphoid cells thanon normal human lymphocytes. The amino sugars glucosamine ormannosamine in the combination caused a synergistic cytotoxiceffect, while the other carbohydrates (N-acetylmannosamine,N-acetylglucosamine, or mannose) had little effect. On the otherhand, the effect of saturated fatty acids (palmitate or stearate)in the same system was nil. An unsaturated fatty acid (oleate)caused an increase in lipid fluidity of the surface membranein MOLT-4 lymphoid cells, which possess higher lipid fluidityin combination with mannosamine, while saturated fatty acidshad no effect on the fluidity properties of the membrane lipids(even in the presence of mannosamine). The relationship betweenmannosamine and unsaturated fatty acids in cytolysis was discussed.     

必需脂肪酸对BEL-7402人肝癌细胞生长和甲胎蛋白分泌抑制的研究

本实验用放射免疫法研究了必需脂肪酸亚麻酸和亚油酸对BEL-7042人肝癌细胞甲胎蛋白(AFP)的分泌的影响,并观察它们对肝癌细胞生长的抑制作用.实验结果表明,42～50μg/ml亚麻酸能明显地抑制肝癌细胞AFP分泌(P<0.01),亚油酸则作用较弱,与对照相比无差异(P>0.05),我们对亚麻酸的抗癌作用的研究为癌症病人的保健和治疗提供实验依据.     

Inhibitory Effect of Dietary Perilla Oil Rich in the n-3 Polyunsaturated Fatty Acid α-Linolenic Acid on Colon Carcinogenesis in Rats

The inhibitory effect of dietary perilla oil rich in the n-3 polyunsaturated fatty acid α-linolenic acid against colon carcinogenesis was investigated in rats. Four groups of 26 F344 rats each received an intrarectal dose of 2 mg of N-methyl-N-nitrosourea 3 times a week for 2 weeks, and received a diet containing 12% perilla oil, 6% or 12% safflower oil (rich in the n-6 polyunsaturated fatty acid linoleic acid), or 12% palm oil (rich in saturated and monounsaturated fatty acids). At week 35, the incidence of colon cancer was significantly lower in perilla oil-fed rats than in other dietary groups; 19% vs. 46%, 56% and 58%. When examined at week 10, the concentration of fecal bile acids, known to be tumor promoters, was not significantly different among the dietary groups, and the intrarectal deoxycholic acid-induced colonic mucosal ornithine decarboxylase activity, a marker of tumor promotion, was significantly lower in perilla oil-fed group than in other groups. The serum and colonic mucosal fatty acid compositions and the blood plasma prostaglandin E₂ level directly reflected the fatty acid composition of each dietary fat. The results suggest that the anti-tumor-promoting effect of dietary perilla oil was a result of a decreased sensitivity of colonic mucosa to tumor promoters arising from the altered fatty acid composition in membrane phospholipid of colonic epithelial cells, and was not a consequence of a decrease of promoters such as bile acids.     

变蓝菌素对口腔鳞癌组织内源性脂肪酸合成活性的影响

[目的]了解谱蓝菌素对口腔鳞癌及口腔正常粘膜内源性脂肪酸合成活性的抑制特点。[方法]切除口腔鳞癌患者新鲜手术标本的癌组织及正常口腔粘膜组织块,将组织块剪成细块,分变蓝菌素处理组与对照组。用[U－^14C]乙酸钠示踪,液体闪烁计数^14C的参入量,以显示脂肪酸合成活性。[结果]口腔鳞癌组织块在变蓝菌素处理1h时脂肪酸合成活性约下降19％,2h下降约64％,4h下降约87％;对照组轻度上升。口腔粘膜在变蓝菌素处理后脂肪酸合成活性略下降,至4h时仅下降20％;对照组略微上升。[结论]变蓝菌素能明显抑制口腔鳞癌组织的内源性脂肪酸合成,但对口腔正常粘膜组织作用轻微,提示口腔鳞癌脂肪酸合成途径有可能成为研发抗肿瘤治疗药物的靶目标。     

Dietary Habits and Physical Activity are Associated With the Risk of Breast Cancer Among Young Iranian Women: A Case-control Study on 1010 Premenopausal Women

Background

Several studies conducted in developed countries introduced diet and physical inactivity as major risk factors for several types of cancers. However, the impact of diet and physical inactivity on the risk of breast cancer (BC) is understudied, and the limited findings are controversial. In addition, no or limited knowledge is available from the developing world.

Effect of fish oil supplementation for 2 generations on changes in macrophage function induced by Walker 256 cancer cachexia in rats

The effect of coconut fat (rich in medium saturated fatty acids) or fish oil (rich in omega-3 polyunsaturated fatty acids) supplementation for 2 generations on tumor growth, cancer cachexia, animal survival and macrophage function was investigated in Walker 256 tumor-bearing rats. Female Wistar rats were supplemented with coconut fat or fish oil prior to mating and then throughout pregnancy and gestation. Both supplementations were daily and orally given at 1 g per kg body weight as a single bolus. Same treatment was performed by the 2 following generations. At 90 days of age, male offspring (50%) from F2 generation were subcutaneously inoculated with 2 x 10(7) Walker 256 tumor cells. At 14 days after tumor implantation, rats not supplemented displayed cancer cachexia characterized by loss of body weight, hypoglycemia, hyperlacticidemia, hypertriglyceridemia, decreased food intake and depletion of glycogen stores in the liver and skeletal muscles. Supplementation with coconut fat did not affect these parameters. However, supplementation with fish oil decreased tumor growth (59%), prevented body weight loss and food intake reduction and attenuated cancer cachexia. In addition, fish oil increased animal survival up to 20 days (from 25% in rats not supplemented to 67% in rats supplemented with fish oil) and improved macrophage function characterized by increased phagocytosis capacity and production of hydrogen peroxide and nitric oxide. These results suggest that fish oil supplementation for 2 generations improves macrophage function in association to reduced tumor growth and attenuated cancer cachexia, maintaining food intake and increasing animal survival.     

Effect of dietary modulation of membrane lipid composition on the thermostability of HTC cells and of a membrane enzyme

Growth of hepatoma tissue culture (HTC) cells in the presence of linoleic (18:2) or arachidonic (20:4) acids for 36 h caused an increased cell thermosensitivity. Plasma membrane-rich fractions were purified (15–20–fold) with high yield (30%) from control and fatty acid-supplemented cells. Contamination with membranes from mitochondria, lysosomes and endoplasmic reticulum was low. Supplementation significantly increased the level of the supplemented fatty acid and decreased the level of oleic acid (18:l) in plasma membrane phospholipids (PL), causing a significant decrease in the oleic acid:PUFA(polyunsaturated fatty acid) ratio. No significant changes occurred in other parameters such as cholesterol:PL, cholesterol:protein or PL:protein ratios. Plasma membranes from PUFA-supplemented cells exhibited a lower membrane order, compared with control cell membranes, as determined by DPH fluorescence polarization over the temperature range 4–40°C. Isothermal inactivation of alkaline phosphodiesterase I in plasma membranes from control and supplemented cells showed curvilinear kinetics. The change in membrane composition and order following supplementation with arachidonic acid was associated with increased thermosensitivity of this enzyme. These data are discussed with respect to the suggestion that the plasma membrane may be a target for cellular thermal injury and death.     

加温对乏氧培养中的舌癌细胞株增殖活性影响的实验研究

目的：探讨加温对乏氧培养中的人舌癌Tca8113细胞株增殖活性的影响，为临床上加温治疗口腔癌提供理论基础。方法：根据是否给予加温处理分为A组(未加温组)和B组(加温组)；根据乏氧时间A、B组又分别分为0h、3h、6h、12h、24h5个小组。依此分组，采用MTT法检测加温对乏氧人舌癌Tca8113细胞增殖活性的抑制率。结果：加温可降低乏氧人舌癌Tca8113细胞的增殖活性；且随着乏氧时间的延长，此作用越明显。结论：乏氧可提高肿瘤细胞对加温的敏感性，为加温联合放、化疗治疗口腔癌提供进一步的理论依据。