Serum adiponectin and leptin levels in Taiwanese breast cancer patients

The role of two adipocytokines, adiponectin and leptin, in Taiwanese breast cancer patients remains to be determined. In this study, we analyzed the correlations between the serum levels of adiponectin and leptin and the various clinicopathological parameters in 100 newly diagnosed, histologically confirmed breast cancer patients and 100 controls. We found serum levels were decreased significantly for adiponectin in the breast cancer patients, in comparison to controls (Student t-test, P=0.003), while serum levels were increased significantly for leptin in the breast cancer patients in comparison to controls (Student t-test, P=0.025). Leptin/adiponectin (L/A ratio) were increased significantly in the breast cancer patients, in comparison to controls (Student t-test, P=0.009). Among the clinicopathological parameters, estrogen receptor, progesterone receptor, HER2/neu, lymph node metastasis, tumor stage, and tumor grade all showed no effect on the serum levels of adiponectin and leptin. BMI was negatively and positively correlated to serum adiponectin and leptin levels, respectively (Spearman's correlation, r=-0.333 and 0.323, respectively; P<0.001 for both). Intriguingly, serum L/A ratio disclosed a positive correlation to tumor size (r=0.21, P=0.036). In summary, our results suggest that low serum adiponectin levels and high serum leptin levels are associated with an increased risk for breast cancer. Also, independent of the effect of BMI, the increased serum ratio of L/A may indicate the presence of aggressive breast cancers.     

Expression of Leptin,Leptin Receptor,Adiponectin, and Adiponectin Receptor in Ductal Carcinoma In Situ and Invasive Breast Cancer

Purpose

Adipocytokines, such as leptin, resistin, and adiponectin, are associated with obesity and breast cancer. Several studies have indicated that adipocytokines may influence tumor growth or differentiation. The aims of this study were to determine the expression of leptin, leptin receptor (ObR), adiponectin and adiponectin receptor (AdipoR) in human breast cancer, to evaluate their prognostic significance in the breast cancer.

Methods

Specimens from 198 patients with primary breast cancer were enrolled, and representative paraffin tumor blocks were selected for constructing tissue microarrarys (TMA). Immunohistochemical staining for leptin, ObR, adiponectin, and AdipoR was performed using TMA, and the clinicopathologic characteristics were evaluated from the patient''s medical records.

Results

Stage 0 breast cancer accounted for 41 cases, and 157 cases were invasive cancer. Positive rates of leptin and ObR expression in the ductal carcinoma in situ (DCIS) group were significantly higher than those of the invasive cancer group (97.4% vs. 34.0%, p<0.001; 74.4% vs. 29.8%, p<0.001). However, positive rates of adiponectin and AdipoR expression in the invasive cancer group were significantly higher than those in the DCIS group (53.7% vs. 33.3%, p=0.024; 59.9% vs. 26.3%, p<0.001). High leptin expression was significantly associated with high Ki-67 expression (p=0.016). High adiponectin expression was significantly correlated with smaller tumor size (p=0.001).

Conclusion

We suggest that losses of leptin and ObR expression could be associated with invasive cancer, whereas high adiponectin and AdipoR expression may be associated with breast cancer invasiveness.     

Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case–control study

Obesity and insulin resistance have been implicated in the etiology of pancreatic cancer (PC). Whether adiponectin and/or leptin, two adipocyte-secreted hormones important in metabolic regulation, are associated with PC pathogenesis and whether adiponectin receptors are expressed in PC remains unknown. In a hospital-based case–control study, we studied 81 cases with incident, histologically confirmed PC and 81 controls matched on gender and age between 2000 and 2007 to investigate the role of adiponectin and leptin adjusting for risk factors linked to PC. In a separate study, we also studied for the first time whether adiponectin receptors 1 and 2 are expressed in PC by studying 16 PC tumor tissue samples which were analyzed using immunohistochemistry. When subjects were divided into control-defined quartiles of adiponectin and leptin, lower leptin but higher adiponectin levels were associated with PC (p = 0.001 and p = 0.05 respectively) before and after controlling for age, gender, BMI, smoking status, alcohol consumption, history of diabetes, and family history of pancreatic cancer. Of the PC tumor tissue samples analyzed, 87.5% had positive or strong positive expression of AdipoR1 and 93.7% had positive or strong positive expression of AdipoR2. Further prospective studies are needed to determine whether the elevated adiponectin and low leptin levels reported in this study reflect compensatory changes during PC progression and thus can be used as markers for PC or whether they are causally implicated in PC.     

The influence of overweight and insulin resistance on breast cancer risk and tumour stage at diagnosis: a prospective study

It is hypothesized that insulin resistance and related metabolic factors may influence breast cancer risk, however the epidemiological evidence remains inconclusive. We conducted a case–control study nested in a prospective cohort in Northern Sweden, to clarify the associations of body mass index (BMI), leptin, adiponectin, C-peptide, and glycated haemoglobin (HbA1c) with breast cancer risk. We also investigated whether these associations may be modified by age at diagnosis, tumour stage, and oestrogen and progesterone receptor status. During follow-up, 561 women developed invasive breast cancer and 561 matched controls were selected. Conditional logistic regression was used to calculate odds ratios (OR) as estimates of relative risk, and 95% confidence intervals (CI). The associations of BMI, leptin and HbA1c with breast cancer risk differed significantly according to whether the tumour was diagnosed as stage I or stage II–IV (P _{heterogeneity} all <0.05). These factors were significantly inversely associated with risk in the group of stage I tumours, with ORs for top vs. bottom tertile for BMI of 0.48 (95% CI, 0.30–0.78, P _trend = 0.004); leptin, 0.64 (95% CI, 0.41–1.00, P _trend = 0.06); and HbA1c, 0.47 (95% CI, 0.28–0.80, P _trend = 0.005). For stage II–IV tumours, there was a suggestion of an increased risk with higher levels of these factors. There were no significant differences in the associations of BMI, leptin, adiponectin, C-peptide and HbA1c with breast cancer risk in subgroups of age at diagnosis or tumour receptor status. This prospective study suggests that BMI, leptin and HbA1c influence breast tumour initiation and progression. Anne E. Cust and Tanja Stocks contributed equally to this work.     

Serum leptin,adiponectin and endometrial cancer risk in Chinese women

Objective

To investigate the relationship between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women.

Methods

We conducted a case-control study of a total of 516 Chinese women to detect the relationships between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women. The study subject constituted 206 cases of endometrial cancer and 310 normal controls.

Results

Patients with endometrial carcinoma had higher serum leptin concentrations than controls (28.8±2.2 ug/L vs. 19.8±1.4 ug/L; p<0.001). The adiponectin levels in patients were lower than in controls with borderline statistical significance (2,330.7±180.5 ug/L vs. 2,583.9±147.2 ug/L; p=0.078). Logistic regression analysis confirmed the associations between leptin or adiponectin, and endometrial carcinoma after adjustment for age, body mass index, fasting insulin, serum glucose, cholesterol, triglycerides, and high-density lipoprotein cholesterol (odds ratio for the top tertile vs. the bottom tertile: leptin 2.05; 95% confidence interval [CI], 1.28 to 3.29; p<0.001; adiponectin 0.52; 95% CI, 0.32 to 0.83; p<0.001).

Conclusion

Increased leptin or decreased adiponectin levels are associated with endometrial carcinoma.     

Integral Role of PTP1B in Adiponectin-Mediated Inhibition of Oncogenic Actions of Leptin in Breast Carcinogenesis

The molecular effects of obesity are mediated by alterations in the levels of adipocytokines. High leptin level associated with obese state is a major cause of breast cancer progression and metastasis, whereas adiponectin is considered a “guardian angel adipocytokine” for its protective role against various obesity-related pathogenesis including breast cancer. In the present study, investigating the role of adiponectin as a potential inhibitor of leptin, we show that adiponectin treatment inhibits leptin-induced clonogenicity and anchorage-independent growth. Leptin-stimulated migration and invasion of breast cancer cells is also effectively inhibited by adiponectin. Analyses of the underlying molecular mechanisms reveal that adiponectin suppresses activation of two canonical signaling molecules of leptin signaling axis: extracellular signal-regulated kinase (ERK) and Akt. Pretreatment of breast cancer cells with adiponectin protects against leptin-induced activation of ERK and Akt. Adiponectin increases expression and activity of the physiological inhibitor of leptin signaling, protein tyrosine phosphatase 1B (PTP1B), which is found to be integral to leptin-antagonist function of adiponectin. Inhibition of PTP1B blocks adiponectin-mediated inhibition of leptin-induced breast cancer growth. Our in vivo studies show that adenovirus-mediated adiponectin treatment substantially reduces leptin-induced mammary tumorigenesis in nude mice. Exploring therapeutic strategies, we demonstrate that treatment of breast cancer cells with rosiglitazone results in increased adiponectin expression and inhibition of migration and invasion. Rosiglitazone treatment also inhibits leptin-induced growth of breast cancer cells. Taken together, these data show that adiponectin treatment can inhibit the oncogenic actions of leptin through blocking its downstream signaling molecules and raising adiponectin levels could be a rational therapeutic strategy for breast carcinoma in obese patients with high leptin levels.     

Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer

Background

Adiponectin is inversely related to BMI, positively correlates with insulin sensitivity, and has anti-atherogenic effects. In recent years, adiponectin has been well studied in the field of oncology. Adiponectin has been shown to have antiproliferative effects on gastric cancer, and adiponectin expression is inversely correlated with clinical staging of the disease. However, no studies have reported the correlation between serum adiponectin and receptor expression with disease progression.

Methods

In this study, we evaluated expression levels of 2 adiponectin receptors--AdipoR1 and AdipoR2--and attempted to correlate their expression with prognosis in gastric cancer patients. AdipoR1 and AdipoR2 expression in gastric cancer cell lines (MKN45, TMK-1, NUGC3, and NUGC4) was evaluated by western blotting analysis, and the antiproliferative potential of adiponectin was examined in vitro. Serum adiponectin levels were evaluated in 100 gastric cancer patients, and the expression of AdipoR1 and AdipoR2 was assessed by immunohistochemical staining.

Results

MKN45 and NUGC3 expressed higher levels of AdipoR1 compared to NUGC4, even though there was no significance in AdipoR2 expression. The antiproliferative effect of adiponectin was confirmed in MKN45 and NUGC3 at 10 μg/ml. No significant associations were observed between serum adiponectin levels and clinicopathological characteristics, but lymphatic metastasis and peritoneal dissemination were significantly higher in the negative AdipoR1 immunostaining group (24/32, p = 0.013 and 9/32, p = 0.042, respectively) compared to the positive AdipoR1 group (lymphatic metastasis, 33/68; peritoneal dissemination, 8/68). On the other hand, AdipoR2 expression was only associated with histopathological type (p = 0.001). In survival analysis, the AdipoR1 positive staining group had significantly longer survival rates than the negative staining group (p = 0.01). However, multivariate analysis indicated that AdipoR1 was not an independent prognostic factor on patient's survival on gastric cancer.

Conclusions

In gastric cancer, adiponectin has the possibility to be involved in cell growth suppression via AdipoR1. The presence of AdipoR1 could be a novel anticancer therapeutic target in gastric cancer.

     

Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case–control study

Accumulating evidence supports a role for obesity in the etiology of multiple myeloma (MM). The distinct possibility exists that obesity may be linked to MM through altered adipokine secretion and circulating levels, one of which, adiponectin, has a protective role in several malignancies, including leukemia. In this case–control study, we investigated the role of serum adiponectin, resistin, and leptin levels in the etiopathogenesis of MM and we explored their association with several established prognostic factors. Seventy three patients with incident, histologically confirmed MM and 73 controls matched on gender and age were studied between 2001 and 2007, and blood samples were collected. Serum adiponectin, leptin, resistin, as well as MM prognostic parameters were determined. Statistical analysis of the data was performed using univariate and multivariate analyses. Lower serum adiponectin and resistin levels were associated with higher risk of MM by bivariate analysis and after adjusting for age, gender, BMI, and serum levels of leptin (p < 0.0001). Adiponectin may have a protective role in MM, whereas leptin was not associated with risk for MM at a comparable level of significance and resistin levels may be decreased via a compensatory mechanism. Further studies are needed to confirm these associations and to explore the mechanisms underlying adiponectin’s role in MM and plasma cell dyscrasias.     

Demonstration of adiponectin receptors 1 and 2 mRNA expression in human breast cancer cells

Recently, we have shown that low adiponectin levels are significantly associated with an increased breast cancer risk. It seems to be very important to study the expression of adiponectin receptor 1 (AdipoR1) and receptor 2 (AdipoR2) in the human breast epithelial cells and breast cancer cells in order to clarify whether or not adiponectin exerts its effects directly on these cells. Expression of adiponectin, AdipoR1, and AdipoR2 mRNA was determined by RT-PCR assay using the RNA samples obtained from human breast cancer cell lines (MCF-7, T47D, SKBR3, and MDA-MB231), HMEC (primary culture of normal human mammary epithelial cells), adipose tissues (axilla) as well as breast cancer cells and normal breast epithelial cells selectively collected from breast cancer tissues by laser microdissection (LMD). Adiponectin mRNA expression was observed only in the adipose tissues. On the other hand, AdipoR1 and AdipoR2 mRNA expression was observed in all four breast cancer cell lines, HMEC, adipose tissues as well as breast cancer cells and normal breast epithelial cells selectively collected by LMD. In addition, AdipoR1 and AdipoR2 expression in both normal breast epithelial cells and breast cancer cells was confirmed by immunohistochemistry. These results suggest a possibility that adiponectin might modulate the growth of normal breast epithelial cells and breast cancer cells directly through AdipoR1 and AdipoR2 receptors, and that the association of low serum adiponectin levels with a high breast cancer risk might be explained, at least in part, by the direct effect of adiponectin on the breast epithelial cells.     

Tissue levels of adiponectin in breast cancer patients

BACKGROUND: Adiponectin is a new adipocyte-secreted protein and associated with insulin-resistant status, such as type 2 diabetes mellitus and obesity. The inverse correlation between serum adiponectin levels and breast cancer risk was recently documented. On the other hand, the association of tissue adiponectin levels with breast cancer has not been previously reported. Thus, in the present study, the relationship between tissue adiponectin levels and breast cancer was evaluated. METHODS: We analyzed the correlation between tissue adiponectin levels and the occurrence of breast cancer in a case-control study comprising 27 women with diagnosed and histologically confirmed breast cancer and 33 women with fibroadenoma. In addition, the association of tissue adiponectin levels with the various classical risk factors, such as body mass index, menopausal status and, tumor size, stage, lymph node status, hormonal status were also studied. RESULTS: Tissue adiponectin levels in patients with breast cancer (0.75 +/- 0.06) were significantly higher than those in controls (0.68 +/- 0.1) (P = 0.02). The high tissue adiponectin levels were associated with significantly (P = 0.001) an increased risk for breast cancer compared with those in the low tissue adiponectin levels (OR, 1.34; 95% CI, 1.12-1.84) in breast cancer patients. In addition, postmenopausal women with the high tissue adiponectin levels showed a significantly (P = 0.003) an increased risk for breast cancer compared with women in low tissue adiponectin levels (OR, 1.63; 95% CI, 1.23-1.90). The correlation between BMI and breast cancer was not found (P > 0.05). Furthermore, the status of estrogen receptor, progesterone receptor, HER-2/neu receptor and lymph nodes involvement were established, no effect on the tissue adiponectin levels in patients with breast cancer and no correlations were detected among tumor stage, tumor size and the levels of tissue adiponectin (P > 0.05). CONCLUSION: Our results suggest that the high tissue adiponectin levels significantly detected in breast cancer patients and associated with an increased risk for breast cancer.     

血清瘦素水平及体质指数与乳腺癌发生的相关性研究

  目的 探讨血清瘦素水平及体质指数与乳腺癌发生的相关性，为乳腺癌的防治寻找科学依据。方法 收集术前乳腺癌患者90例，乳腺良性疾病患者32例，健康对照103例血清，采用放射免疫分析法测定瘦素水平，并进行体质指数的测量与计算。采用SPSS软件包进行统计学处理。结果 乳腺癌组血清瘦素水平与体质指数明显高于乳腺良性疾病和健康对照组，差异均具有统计学意义（P＜0.01）；三组人群瘦素水平与体质指数均呈正相关，相关系数分别为0.327（P＜0.001），0.416（P＜0.001），0.525（P＜0.001）；Logistic回归分析，血清瘦素水平的升高是乳腺癌发生的危险因素，OR值为1.14（95 %CI：1.076 ~ 1.209）。结论 血清瘦素水平、体质指数升高可能与乳腺癌发生有关。     

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.     

脂联素与乳腺癌的相关性

 脂联素是至今发现的惟一与肥胖呈负相关的脂肪细胞特异性蛋白,具有增强胰岛素敏感性、抗动脉硬化、抗炎作用。最近有研究报道,脂联素与多种肥胖相关恶性肿瘤的发生发展密切相关,尤其是绝经后乳腺癌。肥胖是乳腺癌发生的独立危险因素,近来关于脂联素与乳腺癌的关系及其作用机制、信号通路的研究有很大进展。     

血清抵抗素、脂联素和瘦素水平与乳腺癌的相关性研究

目的研究乳腺癌患者抵抗素、脂联素、瘦素及血脂变化及其临床意义。方法 90例经病理诊断为乳腺癌的患者为病例组,50例与之年龄匹配的健康人群为对照组,测定血清中的抵抗素,脂联素、瘦素、空腹血糖（FBG）及血脂。结果病例组脂联素及高密度脂蛋白胆固醇（HDL-C）显著降低（P〈0.01或P〈0.05）。病例组抵抗素、瘦素、空腹血糖及甘油三酯均明显增加（P〈0.01或P〈0.05）。但抵抗素、脂联素及瘦素在绝经前乳腺癌患者与健康对照组之间差异无统计学意义（P〉0.05）。有淋巴结转移的乳腺癌患者与无淋巴结转移乳腺癌患者间,抵抗素、脂联素及瘦素差异有统计学意义（P〈0.01）。逐步回归分析显示,脂联素及HDL的降低,瘦素和抵抗素的升高将会增加罹患乳腺癌的风险。血清中脂联素降低和瘦素的增加与乳腺癌患者淋巴结的转移呈现相关性。结论血清中脂联素水平的降低和抵抗素及瘦素水平的升高是乳腺癌患病的危险因素。血清较低的脂联素和较高的瘦素是乳腺癌转移的危险因素。     

Impact of a mixed strength and endurance exercise intervention on levels of adiponectin, high molecular weight adiponectin and leptin in breast cancer survivors

Abstract  

Evidence suggests that exercise affects breast cancer risk and outcomes, but little is known about the mechanisms through which this effect may be mediated. This study examines the impact of exercise upon levels of adiponectin, high molecular weight adiponectin (HMWA), and leptin in breast cancer survivors.     

瘦素和瘦素受体基因表达与乳腺癌发生发展的关系

目的探讨瘦素和瘦素受体基因表达与乳腺癌发生、发展及临床病理特征之间的关系。方法应用免疫组织化学方法检测132例原发性乳腺癌患者、66例乳腺良性病变患者及30例癌旁正常乳腺组织瘦素和瘦素受体基因的表达。结果瘦素及瘦素受体基因在乳腺癌组织中表达的阳性率分别为76．5％（101／132）和70．5％（92／132）,显著高于乳腺良性病组[56．1％（37／66）和56．1％（37／66）]、癌旁正常组织[46．7％（14／30）、43．3％（13／30）],差异有统计学意义（χ^2=8．72,P=0．003;χ^2=4．04,P=0．044;X。10．57,P=0．001;χ^2=7．94,P=0．005）;乳腺癌组织瘦素和瘦素受体基因的表达具有显著相关性（r=0．307,P〈0．05）;乳腺癌组织瘦素与瘦素受体基因的表达在不同年龄、绝经状态、肿瘤大小、分级、组织学类型、远处转移状况、雌激素受体和孕激素受体的表达状况方面差异均无统计学意义（P〉0．05）;但瘦素基因的表达在淋巴结转移患者中阳性率为91．7％,明显高于无淋巴结转移患者的67．9％,二者比较差异有统计学意义（χ^2=10．65,P=0．002）。结论瘦素和瘦素受体基因表达与乳腺癌的发生、发展有密切的关系,瘦素和瘦素受体可能是乳腺癌发生、发展的促进因子。     

脂联素与肿瘤相关关系的研究现状

脂联素是由脂肪细胞特异分泌的一种生物活性分子,与肥胖、胰岛素抵抗等多种疾病相关。近几年关于脂联素与乳腺癌、子宫内膜癌、子宫平滑肌瘤、白血病、结肠直肠癌、胃癌、前列腺癌等几种恶性肿瘤的相关关系及其作用机制的研究取得了较大的进展。     

Serum Adiponectin Level Association with Breast Cancer Risk: Evidence from a Case-Control Study

Background: Adiponectin is a protein, synthesized by adipose tissue, which has a questionable role in breastcancer pathogenesis. This study focused on serum levels of adiponectin among cases and controls, and its possibleassociation with breast cancer risk. Materials and Methods: This case-control study covered 175 diagnosedbreast cancer patients with positive histopathology from Breast Clinic, surgical unit-1, Civil Hospital, Karachiand 175 healthy controls from various screening programs. Blood samples were obtained after an overnightfast and later analyzed. Results: Fasting blood glucose was significantly raised, while serum adiponectin wassignificantly decreased in breast cancer cases when compared to control subjects. To find the precise influenceof serum adiponectin on the risk of breast cancer, subjects were divided in to quartiles based on serum levelsof adiponectin. It is observed that risk of breast cancer decreased with rising quartile. Q2 (25th-50th) had thehighest OR=1.76 (CI: 0.93- 3.34), Q3 (50th-75th) has OR= 0.89 (CI: 0.48-1.64), while subjects in the highestquartile Q4 (>75th) had significantly (p< 0.05) decreased risk of breast cancer having OR=0.06 (CI: 0.02-0.15),when compared to the lowest quartile. Conclusions: We demonstrated a statistically significant association ofelevated serum adiponectin with decreased risk of breast cancer. This signifies a protective role of adiponectinvia an intricate mechanism of masking mitogenic growth factors in breast carcinogenesis.     

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.