肥胖对淋巴结阳性的乳腺癌患者总生存率的影响

目的:探讨肥胖对淋巴结阳性的乳腺癌患者预后的影响.方法:收集593例淋巴结阳性的女性乳腺癌患者的年龄、绝经状态、家族史、体质量指数(body mass index,BMI)、病理检查及临床治疗资料.用log-rank检验及COX回归分析分别进行影响总生存(overall survival,OS)的单因素和多因素分析;用卡方检验进行肥胖组与非肥胖组间临床病理特征的差异比较.结果:肥胖是影响淋巴结阳性乳腺癌预后的独立不良因素(P=0.003),是影响绝经前患者OS的独立不良预后因素(P=0.010),而对绝经后患者不存在这种影响;肥胖与肿瘤大小具有相关性(P＜0.001).结论:肥胖是影响淋巴结阳性的乳腺癌患者预后的不良因素,尤其是绝经前患者;肥胖患者的肿瘤直径较非肥胖患者的大,这可能是肥胖者预后不良的一个重要原因.     

脂肪细胞因子与乳腺癌

肥胖与绝经后乳腺癌的发病、晚期病变和预后明显相关,绝经后肥胖女性雌激素水乎的升高被认为是其主要的机制之一。脂肪细胞因子是白色脂肪细胞分泌的多种激素和细胞因子,研究发现其与乳腺癌细胞的增殖、浸润、转移和血管生成有关,提示其可能是肥胖与乳腺癌关系的生物学基础。     

脂肪细胞因子与乳腺癌

肥胖与绝经后乳腺癌的发病、晚期病变和预后明显相关,绝经后肥胖女性雌激素水乎的升高被认为是其主要的机制之一。脂肪细胞因子是白色脂肪细胞分泌的多种激素和细胞因子,研究发现其与乳腺癌细胞的增殖、浸润、转移和血管生成有关,提示其可能是肥胖与乳腺癌关系的生物学基础。     

肥胖影响乳腺癌的研究进展

摘 要：研究表明肥胖可能会影响乳腺癌的发病和预后,但是影响机制尚未明确。本文搜集整理了近年来肥胖与不同绝经状态、不同分子亚型乳腺癌之间发病和预后的关系研究。其中肥胖对绝经前和绝经后乳腺癌的影响是不同的,同时肥胖对不同分子亚型乳腺癌患者发病和预后的影响亦是不同的,并且肥胖合并糖尿病等其他疾病也导致乳腺癌的预后更差。本文对这些文献加以总结并搜集了一些肥胖对乳腺癌发病机制影响的相关研究,可对肥胖与乳腺癌之间关系的基础研究和临床工作提供更多的参考依据。     

脂肪因子在肿瘤治疗中的研究进展

肥胖是多种肿瘤发生的高危因素, 在肥胖促进肿瘤发生、发展的过程中, 脂肪组织分泌的脂肪因子扮演着重要的角色。不同的脂肪因子通过其各自的信号通路发挥着促癌或抑癌作用。调整生活方式控制体质量或者靶向脂肪因子及其受体, 是肿瘤治疗领域的一大研究方向, 但目前多数因子还处于基础研究及临床前研究阶段, 有关各种脂肪因子促癌或抑癌的分子机制还待进一步探索, 同时双重抑制剂及联合疗法是未来脂肪因子用于肿瘤治疗的重点研究策略。     

肥胖,体脂肪分布和乳腺癌

多数学者的研究认为乳腺癌的发生和发展不但与肥胖有关，与体脂肪分布也有肯定关系，本文对其近年来的研究加以综述。     

肥胖与乳腺癌关系的研究进展

乳腺癌目前已成为全球女性最常见的恶性肿瘤之一,其发病率和死亡率在女性恶性肿瘤中位居第二。大量临床研究和流行病学资料已证实肥胖与乳腺癌的发生、发展密切相关,其发病机制可能涉及雌激素、胰岛素、胰岛素样生长因子-1（IGF-1）、瘦素、脂联素、炎症因子等多种肥胖相关因子。近年来的研究对肥胖促进乳腺癌发展的机制进行了深入分析,并进一步了解到肥胖对乳腺癌的诊断结果、肿瘤特点、治疗以及预后可产生重要影响。因此,控制体重可能是预防复发转移的积极措施,维持正常体重有助于乳腺癌的防治。     

乳腺

腋窝脂肪抽吸术在腋淋巴结清扫术中的临床应用；不同手术方式对乳腺癌患者术后生存质量及婚姻质量的影响；来曲唑治疗绝经后晚期转移性乳腺癌疗效观察；星状神经节阻滞在防治乳腺癌术后皮下积液中的应用；青年乳腺癌临床特征与预后的分析.     

代谢综合征与乳腺癌的发生与预后

阐述代谢综合征(中心性肥胖、高胰岛素血症或高血糖、血脂异常及高血压)与乳腺癌发生及预后的关系。中心性肥胖增加乳腺癌发生风险,且与乳腺癌的不良预后相关。高胰岛素血症及高血糖是代谢综合征的中心特征,是增加罹患乳腺癌风险的潜在因素,且与乳腺癌不良预后相关。血脂异常与乳腺癌的发生相关,不同血脂成分对于乳腺癌预后的作用不同。高血压是绝经后女性乳腺癌发生的独立预测指标,与乳腺癌预后关系尚不明确,但控制血压有利于乳腺癌患者生存。代谢综合征与乳腺癌发生、预后相关。通过多种途径相互作用。应通过生活方式、饮食习惯的调整防止个体代谢异常发生,从而减少乳腺癌的发生风险。     

超重及肥胖急性白血病患者血清中脂肪素表达的研究

目的 研究肥胖、超重对急性白血病患者血清中脂肪素的表达及预后的影响.方法 收集2008年7月至2015年7月在辽宁省人民医院和中国医科大学附属盛京医院治疗的急性白血病患者570例,根据体质量指数(BMI)分为肥胖/超重组(BMI≥24 kg/m2)和正常体质量组(BMI<24 kg/m2),采用双抗体夹心亲和素-生物素复合酶联免疫吸附试验(ABC-ELISA)检测脂肪素水平,t检验比较两组间血清脂联素、 瘦素和抵抗素表达水平的差异;Kaplan-Meier法比较两组患者间生存情况的差异.结果 急性淋巴细胞白血病(ALL)和急性髓系白血病(AML)肥胖/超重组血清脂联素表达水平均低于正常体质量组[ALL成年组(3.8±2.1)pg/ml比(6.4±2.9)pg/ml,儿童组(4.2±2.7)pg/ml比(7.4±3.1)pg/ml);AML(4.1±2.3)pg/ml比(6.9±3.1)pg/ml](t值分别为-2.291、-2.462、-2.244,均P<0.05);ALL儿童患者肥胖/超重组瘦素表达水平较正常体质量组升高[(34±17)pg/ml比(21±17)pg/ml,t=2.092,P=0.038];所有急性白血病患者肥胖/超重组与正常体质量组间抵抗素表达水平比较,差异均无统计学意义(均P>0.05).Kaplan-Meier生存分析结果显示,AML和ALL成年患者肥胖/超重组5年总生存率均低于正常体质量组(38.0％比46.6％,χ2=1.449,P=0.001;41.4％比48.4％,χ2=4.166,P=0.041).结论对于急性白血病患者,肥胖、超重者血清脂联素水平降低,肥胖、超重的成年ALL及AML患者的5年总生存率较正常体质量患者低.     

Serum Adiponectin but not Leptin at Diagnosis as a Predictor of Breast Cancer Survival

Limited numbers of epidemiological studies have examined the relationship between adipokines and breast cancer survival. Preoperative serum levels of obesity-related adipokines (leptin and adiponectin) were here measured in 370 breast cancer patients, recruited from two hospitals in Korea. We examined the association between those adipokines and disease-free survival (DFS). The TNM stage, ER status and histological grade were aslo assessed in relation to breast cancer survival. Elevated adiponectin levels were associated with reducedDFS of breast cancer (Ptrend=0.03) among patients with normal body weight, predominantly in postmenopausal women. There was no association of leptin with breast cancer survival. In conclusion, our study suggests that high levels of adiponectin at diagnosis are associated with breast cancer survival among women with normal body weight.     

Adipose‐Derived Fatty Acid‐Binding Proteins Plasma Concentrations Are Increased in Breast Cancer Patients

Background

Adipose tissue is an endocrine organ that could play a role in tumor progression via its secreted adipokines. The role of adipose‐derived fatty acid‐binding protein (FABP) 4 and FABP5 in breast cancer is presently under study, but their circulating levels in this pathology are poorly known. We analyzed the blood concentrations of FABP4 and FABP5 in breast cancer patients to determine whether there is an association between them and breast cancer.

Materials and Methods

We studied 294 women in the oncology department with a family history of breast cancer; 198 of the women had breast cancer, and 96 were healthy controls. The levels of FABP4, FABP5, lipid profile, standard biochemical parameter, and high‐sensitivity C‐reactive protein (hsCRP) were determined. We analyzed the association of FABP4 and FABP5 with breast cancer, while adjusting for demographic, anthropometric, and biochemical parameters.

Results

Breast cancer patients had a 24.8% (p < .0001) and 11.4% (p < .05) higher blood concentration of FABP4 and FABP5, respectively. Fatty acid‐binding protein 4 was positively associated with age, body mass index (BMI), FABP5, very‐low‐density lipoprotein cholesterol (VLDLc), non‐high‐density lipoprote in cholesterol (non‐HDLc), Apolipoprotein B 100 (ApoB100), triglycerides, glycerol, glucose, and hsCRP (p < .05), and was negatively associated with HDLc (p < .005) in breast cancer patients. Fatty acid‐binding protein 5 was positively associated with BMI, FABP4, VLDLc, triglycerides, glycerol, and hsCRP (p < .05), and was negatively associated with HDLc and Apolipoprotein AI (ApoAI) (p < .05) in breast cancer patients. Using a logistic regression analysis and adjusting for age, BMI, hsCRP, non‐HDLc, and triglycerides, FABP4 was independently associated with breast cancer (odds ratio [OR]: 1.091 [95% CI: 1.037–1.149]). Moreover, total cholesterol, VLDLc, non‐HDLc, ApoB100, triglycerides, and hsCRP were significantly increased in breast cancer patients (p < .005). In contrast, the non‐esterified fatty acids concentrations were significantly decreased in breast cancer patients (p < .05).

Conclusion

Circulating FABP4 and FABP5 levels were increased in breast cancer patients compared with controls. The positive association of FABP4 with breast cancer was maintained after adjusting for important covariates, while the association with FABP5 was lost. Our data reinforce the role of adipose tissue and their adipokines in breast cancer. Despite these data, further studies must be performed to better explain the prognosis or diagnostic value of these blood parameters and their possible role in breast cancer.

Implications for Practice

We focus on the effect of adipose tissue on cancer, which is increasingly recognized. The association between adipocyte‐derived adipokines and breast cancer opens new diagnosis and therapy perspectives. In this study, we provide original data concerning FABP4 and FABP5 plasma concentrations in breast cancer patients. Compared to control group, breast cancer patients show higher FABP4 and FABP5 blood levels. Our data suggest that, particularly, circulating FABP4 levels could be considered a new independent breast cancer biomarker. Our work translates basic science data to clinic linking the relationship between adipose tissue and lipid metabolism to breast cancer.     

Influence of obesity on breast cancer receptor status and prognosis

Pre-existing obesity and postoperative weight gain are related to a poor prognosis in breast cancer regardless of menopausal status. Delayed diagnosis may be one cause, but of more biological significance, especially in younger women, is the association of adiposity with estrogen receptor-negative tumors with a propensity for distant metastasis. After the menopause, the major mechanism for the relationship is the elevated estrogen synthesis by adipose tissue; these hormone-dependent tumors are estrogen receptor-positive. Insulin and some adipokines also stimulate breast cancer growth and metastasis, both directly and most probably by enhanced angiogenesis. Weight control is important, not only to target breast cancer progression, but also to reduce the risk of nonbreast cancer mortality risk associated with excess adiposity.     

分子标志物预测乳腺癌治疗疗效的研究进展

乳腺癌是多种基因发生突变所导致的复杂疾病,尽早检出预后不佳的高危病人,及时给予合理的治疗,对于改善乳腺癌病人的预后有重要意义。本文通过综合国内外近年来发表的有代表性的有关乳腺癌分子标志物的文献资料,对乳腺癌预后分子标志物的研究进展进行总结,探讨这些分子标志物与乳腺癌治疗疗效及预后的关系。     

分子标志物预测乳腺癌治疗疗效的研究进展

乳腺癌是多种基因发生突变所导致的复杂疾病,尽早检出预后不佳的高危病人,及时给予合理的治疗,对于改善乳腺癌病人的预后有重要意义.本文通过综合国内外近年来发表的有代表性的有关乳腺癌分子标志物的文献资料,对乳腺癌预后分子标志物的研究进展进行总结,探讨这些分子标志物与乳腺癌治疗疗效及预后的关系.     

Hormones of adipose tissue and their biologic role in lung cancer

Introduction

Adipose tissue secretes numerous bioactive peptides, collectively termed “adipocytokines” or “adipokines”. Adipokines act in a paracrine, autocrine, or endocrine manner and regulate several physiological and pathological processes. Increasing evidence indicates that adipokines are implicated also in several malignancies, including lung cancer as well.

Aim

The aim of this study is to summarize data concerning adipokines in lung cancer pathogenesis, prognosis and survival; the role of adipokines in lung cancer cachexia is also examined.

Materials and Methods

A systematic literature search was performed in the electronic database of Medline. Several studies and review articles met the inclusion criteria.

Results

Leptin and adiponectin are the best studied adipokines. The majority of the relevant studies has investigated the potential correlations mainly between leptin, adiponectin, and sometimes also resistin, and nutritional status, systemic inflammation of lung cancer or lung cancer cachexia and have also assessed their prognostic significance. Few other studies have studied genetic variations in leptin, leptin receptor and adiponectin genes and their association with lung cancer susceptibility and prognosis. The ongoing list of adipokines associated with lung cancer also includes resistin, chemerin, and visfatin.

Conclusions

Increasing evidence points to the involvement of certain adipocytokines in lung cancer development, progression and prognosis. No conclusive evidence exists so far with regards to the role of adipocytokines in lung cancer cachexia. Future, longitudinal studies are warranted in order to clarify the role of adipocytokines in lung cancer and also uncover adipocytokines as novel therapeutic targets.     

Obesity and breast cancer: status of leptin and adiponectin in pathological processes

It is well recognized that obesity increases the risk of various cancers, including breast malignancies in postmenopausal women. Furthermore, obesity may adversely affect tumor progression, metastasis, and overall prognosis in both pre- and postmenopausal women with breast cancer. However, the precise mechanism(s) through which obesity acts is/are still elusive and this relationship has been the subject of much investigation and speculation. Recently, adipose tissue and its associated cytokine-like proteins, adipokines, particularly leptin and adiponectin, have been investigated as mediators for the association of obesity with breast cancer. Higher circulating levels of leptin found in obese subjects could be a growth-enhancing factor as supported by in vitro and preclinical studies, whereas low adiponectin levels in obese women may be permissive for leptin’s growth-promoting effects. These speculations are supported by in vitro studies which indicate that leptin promotes human breast cancer cell proliferation while adiponectin exhibits anti-proliferative actions. Further, estrogen and its receptors have a definite impact on the response of human breast cancer cell lines to leptin and adiponectin. More in-depth studies are needed to provide additional and precise links between the in vivo development of breast cancer and the balance of adiponectin and leptin.     

Expression of a CD44 variant and VEGF-C and the implications for lymphatic metastasis and long-term prognosis of human breast cancer

The aim of the present study was to determine whether expression of the CD44 variant v7-v8 (CD44v7-v8) or vascular endothelial growth factor-C (VEGF-C) is associated with long-term prognosis in breast cancer patients. A 10-year follow-up of 91 patients with primary breast cancer who were previously assessed for CD44 expression was undertaken. Immunohistochemical evaluation of VEGF-C expression was performed in 87 of these patients and their long-term prognosis was assessed. The disease-free and overall survival rates were significantly poorer for the CD44v7-v8-positive patients than for the patients negative for this marker. VEGF-C expression was detected in 38 out of the 87 patients (43.7%) with primary human breast cancer. There were no significant differences in tumor size, histological type, axillary lymph node status, presence of lymphatic or venous invasion, or presence of estrogen receptors and progesterone receptors between the VEGF-C-positive and -negative patients. There were also no significant differences in the disease-free or overall survival rates in these patient groups. In conclusion after the 10-year follow-up, expression of CD44v7-v8 was associated with poor prognosis for breast cancer patients. However, there was no association between VEGF-C expression and the clinicopathological factors or prognosis of breast cancer patients.     

An ex vivo co‐culture model system to evaluate stromal–epithelial interactions in breast cancer

Breast cancer is the most commonly diagnosed cancer among women worldwide. High breast cancer incidence and mortality rates, especially in obese patients, emphasize the need for a better biological understanding of this disease. Previous studies provide substantial evidence for a vital role of the local extracellular environment in multiple steps of tumor progression, including proliferation and invasion. Current evidence supports the role of adipocytes as an endocrine organ, which produces steroid hormones, pro‐inflammatory cytokines and adipokines, such as leptin. To further define the role of the mammary microenvironment on tumorigenesis, we have developed an adipose‐tumor epithelial cell co‐culture system designed to reproduce the in vivo mammary environment. We validate this model through use of coherent anti‐Stokes Raman scattering (CARS) microscopy, a label‐free vibrational imaging technique. CARS analysis demonstrates the sustained viability of the adipocytes, and that mammary cancer cell morphology parallels that of tumors in vivo. Also, characterized was the influence of mammary adipose tissue on tumor cell growth and migration. Adipose tissue co‐cultured with mammary tumor epithelial cells, in the absence of any serum or supplemental growth factors, resulted in substantial increases in growth and migration of tumor cells. In conclusion, this novel co‐culture system provides an ideal model to study epithelial–stromal interactions in the mammary gland. Understanding the relationship between adipose tissue, the most abundant and least studied component of the breast stroma and tumor epithelial cells is critical to clarifying the influence of obesity on the development, progression and prognosis of breast cancer.