The regulation of MFG-E8 on the mitophagy in diabetic sarcopenia via the HSPA1L-Parkin pathway and the effect of D-pinitol.

BACKGROUND: Diabetic sarcopenia is a disease-related skeletal muscle disorder that causes progressive symptoms. The complete understanding of its pathogenesis is yet to be unravelled, which makes it difficult to develop effective therapeutic strategies. This study investigates how MFG-E8 affects mitophagy and the protective role of D-pinitol (DP) in diabetic sarcopenia. METHODS: In vivo, streptozotocin-induced diabetic SAM-R1 (STZ-R1) and SAM-P8 (STZ-P8) mice (16-week-old) were used, and STZ-P8 mice were administrated of DP (150 mg/kg per day) for 6 weeks. Gastrocnemius muscles were harvested for histological analysis including transmission electron microscopy. Proteins were evaluated via immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) assay. In vitro, advanced glycation end products (AGEs) induced diabetic and D-galactose (DG) induced senescent C2C12 models were established and received DP, MFG-E8 plasmid (Mover)/siRNA (MsiRNA), or 3-MA/Torin-1 intervention. Proteins were evaluated by IF and WB assay. Immunoprecipitation (IP) and co-immunoprecipitation (CO-IP) were used for hunting the interacted proteins of MFG-E8. RESULTS: In vivo, sarcopenia, mitophagy deficiency, and up-regulated MFG-E8 were confirmed in the STZ-P8 group. DP exerted protective effects on sarcopenia and mitophagy (DP + STZ-P8 vs. STZ-P8; all P < 0.01), such as increased lean mass (8.47 ± 0.81 g vs. 7.08 ± 1.64 g), grip strength (208.62 ± 39.45 g vs. 160.87 ± 26.95 g), rotarod tests (109.7 ± 11.81 s vs. 59.3 ± 20.97 s), muscle cross-sectional area (CSA) (1912.17 ± 535.61 µm2 vs. 1557.19 ± 588.38 µm2), autophagosomes (0.07 ± 0.02 per µm2 vs. 0.02 ± 0.01 per µm2), and cytolysosome (0.07 ± 0.03 per µm2 vs. 0.03 ± 0.01 per µm2). DP down-regulated MFG-E8 in both serum (DP + STZ-P8: 253.19 ± 34.75 pg/mL vs. STZ-P8: 404.69 ± 78.97 pg/mL; P < 0.001) and gastrocnemius muscle (WB assay. DP + STZ-P8: 0.39 ± 0.04 vs. STZ-P8: 0.55 ± 0.08; P < 0.01). DP also up-regulated PINK1, Parkin and LC3B-II/I ratio, and down-regulated P62 in gastrocnemius muscles (all P < 0.01). In vitro, mitophagy deficiency and MFG-E8 up-regulation were confirmed in diabetic and senescent models (all P < 0.05). DP and MsiRNA down-regulated MFG-E8 and P62, and up-regulated PINK1, Parkin and LC3B-II/I ratio to promote mitophagy as Torin-1 does (all P < 0.05). HSPA1L was confirmed as an interacted protein of MFG-E8 in IP and CO-IP assay. Mover down-regulated the expression of Parkin via the HSPA1L-Parkin pathway, leading to mitophagy inhibition. MsiRNA up-regulated the expression of PINK1 via SGK1, FOXO1, and STAT3 phosphorylation pathways, leading to mitophagy stimulation. CONCLUSIONS: MFG-E8 is a crucial target protein of DP and plays a distinct role in mitophagy regulation. DP down-regulates the expression of MFG-E8, reduces mitophagy deficiency, and alleviates the symptoms of diabetic sarcopenia, which could be considered a novel therapeutic strategy for diabetic sarcopenia.

A novel predictor for the use of concurrent chemotherapy in early-stage cervical cancer with intermediate-risk factors.

Objective: For early-stage cervical cancer patients experiencing radical surgery, postoperative radiotherapy was recommended for patients with a combination of intermediate-risk factors. However, there was no consensus on whether to administer concurrent chemotherapy. The aim of the study was to confirm the clinical value of the controlling nutritional status (CONUT) score in guiding the use of concurrent chemotherapy during postoperative radiotherapy. Methods: A total of 969 patients with FIGO stage IB-IIA cervical cancer were retrospectively analyzed. Kaplan-Meier survival analysis was performed to compare disease-free survival (DFS) and cancer-specific survival (CSS) rates between different group. A Cox proportional hazards regression test was used to conduct multivariate analyses. Results: For the patients in the high CONUT group (≥3), the addition of concurrent chemotherapy had better 5-year DFS (91.2 % vs. 72.8 %, P = 0.005) and CSS (93.8 % vs. 77.4 %, P = 0.013) than those without it. Meanwhile, the patients with concurrent chemotherapy had less rate of locoregional recurrence (8.5 % vs 16.7 %, P = 0.034) and distant metastases (11.7 % vs 30.4 %, P = 0.015). The multivariate analysis showed that concurrent chemotherapy was detected to be a factor significantly associated with DFS (P = 0.011), local control (P = 0.041), distant metastasis (P = 0.005) and CSS (P = 0.023). For the patients in low CONUT group (<3), there was no difference in prognosis between patients. Conclusion: Pretreatment CONUT score may be a predictive factor for the use of concurrent chemotherapy in early-stage cervical cancer with intermediate-risk factors during postoperative radiotherapy, and it can be helpful to determine the adjuvant treatment scheme.

The effectiveness of consolidation chemotherapy in high-risk early-stage cervical cancer patients following concurrent chemoradiation after radical surgery.

OBJECTIVE: Studies determining which early-stage cervical cancer patients with high-risk factors benefit from consolidation chemotherapy after postoperative concurrent chemoradiotherapy (CCRT) are limited and inconsistent. The aim of this study was to evaluate the value of consolidation chemotherapy in early-stage cervical cancer. METHODS: From 2010 to 2019, a retrospective review was conducted among high-risk early-stage cervical cancer patients who were treated with postoperative CCRT or consolidation chemotherapy after postoperative CCRT. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 293 patients with early-stage cervical cancer were included in this study. A total of 188 patients were in the consolidation chemotherapy group, and 105 patients were in the postoperative CCRT alone group. The median follow-up was 48.3 months (range: 3-123 months). In the survival analyses, no significant differences in DFS (P = 0.21) or OS (P = 0.15) were observed between the groups. The grade 3-4 leukopenia and neutropenia rates in the consolidation group were higher than those in the concurrent chemoradiotherapy alone group (54.8% vs. 28.6%, P = 0.02; 49.4% vs. 10.5%, P = 0.001, respectively). For patients with ≥2 positive lymph nodes or ≥2 high-risk factors, consolidation chemotherapy significantly improved DFS (P = 0.013 and P = 0.002) and OS (P < 0.001 and P < 0.001) compared with CCRT alone. CONCLUSION: For early-stage cervical cancer, consolidation chemotherapy after postoperative CCRT improved survival outcomes in patients with ≥2 positive lymph nodes or ≥2 high-risk factors.

A Novel Risk Factor for Para-Aortic Lymph Node Recurrence After Definite Pelvic Radiotherapy in Stage IIIB Cervical Cancer.

Background: Studies determining which patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIB disease benefit from prophylactic extended-field irradiation (EFRT), which can reduce para-aortic lymph node (PALN) failure rates, are limited. The study was designed to evaluate the value of the controlling nutritional status (CONUT) score as a risk factor for predicting PALN recurrence and identifying potential indications of prophylactic EFRT. Methods: From 2010 to 2015, a retrospective review was conducted among patients with FIGO stage IIIB cervical cancer who were treated with definitive pelvic radiotherapy or concurrent chemoradiotherapy. We analyzed para-aortic lymph node metastasis-free survival (PALNMFS) using Kaplan-Meier curves. Multivariate analyses were performed using Cox regression models. Results: A total of 116 patients with FIGO stage IIIB cervical cancer were included in the study and the median follow-up was 42.2 months (range: 3.5-104.2 months). Multivariate analysis revealed that the CONUT score (HR: 3.141; 95% CI: 2.321-5.436; P < .001) and ≥3 pelvic lymph node metastases (HR: 2.235; 95% CI: 1.428-11.242; P < .001) were independent risk predictors of PALNMFS. Compared with the low CONUT group (score<3), the high CONUT group (score≥3) was associated with a significantly worse 3-year disease-free survival rate (46.9 vs 69.5%, P = .001), a significantly lower 3-year overall survival rate (68.5 vs 79.7%, P = .016) and a significantly lower PALNMFS rate (74.8 vs 96.4%, P < .001). Conclusions: A high CONUT score (score≥3) and ≥3 pelvic metastatic lymph nodes were significant predictors of PALNMFS after pelvic radiation in FIGO stage IIIB cervical cancer patients. Patients with these risk factors might benefit from prophylactic EFRT.

Pretreatment Squamous Cell Carcinoma Antigen (SCC-Ag) as a Predictive Factor for the Use of Consolidation Chemotherapy in Cervical Cancer Patients After Postoperative Extended-Field Concurrent Chemoradiotherapy.

Objective: The goal of this study was to confirm the clinical value of pretreatment serum squamous cell carcinoma antigen (SCC-Ag) in the administration of consolidation chemotherapy in patients with cervical cancers undergoing postoperative extended-field radiotherapy (EFRT) and concurrent chemotherapy (CCRT). Methods: Between 2007 and 2018, a total of 113 patients were treated with postoperative extended-field intensity-modulated radiotherapy (EF-IMRT) and CCRT. There were 63 patients receiving extended-field concurrent chemoradiotherapy (EF-CCRT) and consolidation chemotherapy, while another 50 patients underwent EF-CCRT alone. For the planning target volume, the prescribed dose was 45 to 50.4Gy/25 to 28 fractions. The consolidation chemotherapy regimen contained docetaxel and cisplatin. Results: For the patients with high pretreatment SCC-Ag, the addition of consolidation chemotherapy significantly improved their treatment outcomes and they had better 5-year overall survival (OS) (81.02% vs 63.44%, P = .018) and disease-free survival (DFS) (76.95% vs 61.12%, P = .007) than those without it. Meanwhile, the patients with consolidation chemotherapy had a lower rate of distant metastasis (8.8% vs 34.8%, P = .001). For the patients with low pretreatment SCC-Ag, there was no difference in prognosis between patients receiving consolidation chemotherapy and those not receiving consolidation. In multivariate analysis, consolidation chemotherapy was found to be a factor significantly associated with DFS (P = .035, 95% confidence interval (CI): 0.304-0.977) and distant metastasis (P = .009, 95% CI: 0.125-0.841). Conclusion: The patients who received consolidation chemotherapy showed significantly better DFS. Furthermore, pretreatment serum SCC-Ag > 6.5 ng/mL may be a predictive factor for the use of consolidation chemotherapy in cervical cancer patients treated with postoperative EF-CCRT.

Preoperative controlling nutritional status (CONUT) score is a prognostic factor for early-stage cervical cancer patients with high-risk factors.

OBJECTIVE: The goal of the study was to confirm whether preoperative controlling nutritional status (CONUT) was a prognostic factor in early-stage cervical cancer patients with high-risk factors after surgery and postoperative concurrent chemoradiotherapy (CCRT). METHODS: Between 2004 and 2015, a total of 698 patients who were treated with surgery and postoperative CCRT were included in this retrospective study. The prescribed dose for postoperative radiotherapy was 45-50.4 Gy in 25-28 fractions and the concurrent chemotherapy regimen contained cisplatin or paclitaxel. Based on the receiver operating characteristic (ROC) analysis, the patients were classified into low (<3) and high (≥3) CONUT groups. RESULTS: Of all study patients, 471 (67.5%) patients were included in the low CONUT group. The low CONUT group had significantly better 5-year disease-free survival (DFS) and overall survival (OS) than the high CONUT group (p<0.001 and p = 0.001, respectively). A high CONUT score was significantly associated with lymph node metastasis, parametrial invasion, and poorer nutritional status, including lower body mass index (BMI) and lower prognostic nutritional index (PNI) score (p<0.05, respectively). The CONUT score was an independent predictor of DFS and OS in multivariate analysis. Notably, the CONUT score still efficiently stratified DFS in the high PNI score group (P = 0.001). CONCLUSIONS: The preoperative high CONUT scores indicated poor prognosis for early-stage cervical cancer patients with high-risk factors treated with surgery and postoperative CCRT. In clinical practice, patients with high CONUT score should be considered to receive consolidation chemotherapy.

Post-operative small pelvic intensity-modulated radiation therapy for early-stage cervical cancer with intermediate-risk factors: efficacy and toxicity.

OBJECTIVE: The aim of the present study was to retrospectively evaluate the toxicity and efficacy of post-operative small pelvic intensity-modulated radiotherapy in early-stage cervical cancer patients with intermediate-risk factors. METHODS: Between 2012 and 2016, 151 patients who had cervical cancer (International Federation of Gynecology and Obstetrics stage I-IIA) with intermediate-risk factors were treated with post-operative small pelvic intensity-modulated radiotherapy. The median dose of 50.4 Gy in 28 fractions with small pelvic intensity-modulated radiotherapy was prescribed to the planning target volume. The intensity-modulated radiotherapy technique used was conventional fixed-field intensity-modulated radiotherapy or helical tomotherapy. RESULTS: The median follow-up was 37 months. The 3-year disease-free survival and overall survival rates were 89 and 96%, respectively. A total of 144 patients (95.3%) were alive at the last follow-up. In total, 6 patients (3.9%) had recurrence: locoregional recurrence in 3 patients (2%), distant metastasis in 2 (1.3%), and both in 1 (0.6%). Diarrhoea was the most common acute toxicity. There were no patients suffering from acute or late grade ≥ 3 toxicity. Only 4 patients (2.6%) had late grade 2 toxicities. CONCLUSIONS: For early-stage cervical cancer patients with intermediate-risk factors, post-operative small pelvic intensity-modulated radiotherapy was safe and well tolerated. The rates of acute and late toxicities were quite satisfactory.

Effects of D-pinitol on myocardial apoptosis and fibrosis in streptozocin-induced aging-accelerated mice.

Diabetic cardiomyopathy (DCM) causes heart failure and increases the mortality in diabetic patients. Myocardial apoptosis and fibrosis are the main features of DCM and aging. The aim is to study the underlying mechanism of D-pinitol (DP) on myocardial apoptosis and fibrosis in an elderly diabetic mouse model. The diabetic model was established by SAMP-8 mice that were injected with streptozotocin daily for five consecutive days. The mice were administrated of DP (150 mg kg-1  day-1 ) by gavage for 10 weeks. The common metabolic disorder indices, cardiac dysfunction, oxidative stress, myocardial apoptosis and fibrosis, and PI3K/Akt/mTOR pathway were investigated. Our findings suggested that DP has a protective effect on DCM, which may be related to regulating oxidative stress, and PI3K/Akt/mTOR pathway involving cardiac fibrosis and apoptosis. DP may be a novel clinical application in fighting against DCM. PRACTICAL APPLICATIONS: D-pinitol (DP) was found in large quantities in soybean and legume foods. DP has a variety of functions, including hypoglycemic, anti-oxidation, anti-inflammatory, cardioprotective, and anti-tumor activity. We used the streptozotocin-induced SAMP8 mice as the diabetic model and treated with DP. We found that DP can improve cardiac dysfunction and inhibits the oxidative stress, myocardial apoptosis and fibrosis. DP has a significant effect on diabetic cardiomyopathy (DCM). The molecular mechanisms are related to regulating oxidative stress, and PI3K/Akt/mTOR pathway involving cardiac fibrosis and apoptosis. DP can prevent and/or delay the onset of DCM.

Definitive extended field intensity-modulated radiotherapy and concurrent cisplatin chemosensitization in the treatment of IB2-IIIB cervical cancer.

OBJECTIVE: To assess the toxicity of delivering extended field intensity-modulated radiotherapy (EF-IMRT) and concurrent cisplatin chemotherapy for locally advanced cervical carcinoma. METHODS: Forty-five patients who underwent EF-IMRT and concurrent cisplatin chemotherapy for the treatment of stage IB2 to IIIB cervical cancer were retrospectively reviewed. The clinical target volume included all areas of gross and potentially microscopic disease and regional lymph node regions. All patients underwent high-dose-rate brachytherapy. The acute and late toxicity were scored using the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively. RESULTS: The median follow-up was 28 months (range, 5 to 62 months). Forty-two patients had a complete response, and three had a persistent disease. Of those 42 patients, 15 patients (35.7%) had recurrence. The regions of recurrence were in-field in 2 patients and out-field in 13 patients. Acute grade ≥3 gastrointestinal, genitourinary and hematologic toxicity occurred in 3, 1, and 9 patients, respectively. Three patients (6.7%) suffered from late grade 3 toxicities. Seven patients experienced ovarian transposition, 5 of those patients (71%) maintained ovarian function. Thirty-eight patients (84.4%) were alive at the last follow-up. CONCLUSION: Concurrent cisplatin chemotherapy with EF-IMRT was safe. The acute and late toxicities are acceptable. EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition.

Extended-field intensity-modulated radiotherapy and concurrent cisplatin-based chemotherapy for postoperative cervical cancer with common iliac or para-aortic lymph node metastases: a retrospective review in a single institution.

OBJECTIVE: Retrospectively, to assess the toxicity of delivering postoperative extended-field intensity-modulated radiotherapy (EF-IMRT) and concurrent cisplatin chemotherapy for patients with cervical cancer with a pathologically confirmed positive common iliac node and/or a para-aortic node. METHODS: Each patient received postoperative EF-IMRT and concurrent cisplatin chemotherapy. The clinical target volume included regional lymph node regions (obturator; common, internal, and external iliac nodal regions; presacral region; and para-aortic regions) and the upper 2.0 cm of the vagina and paravaginal soft tissue lateral to the vagina. The acute and late toxicity were scored using the Common Terminology Criteria for Adverse Events (CTCAE) and the Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively. RESULTS: Fifty-eight patients were treated with postoperative EF-IMRT and concurrent cisplatin chemotherapy. The median follow-up was 34 months. Eighteen patients (31%) had recurrence. The region of recurrence was in-field in 2 patients (3.4%) and out-field in 16 patients (27.6%). Acute grade 3 or higher gastrointestinal, genitourinary, and hematologic toxicity occurred in 2, 1, and 11 patients, respectively. Three patients (5.1%) had late grade 3 toxicities. Thirteen patients experienced ovarian transposition; of these, 10 patients (77%) maintained ovarian function. Forty-one patients (71%) were alive at the last follow-up. CONCLUSIONS: Concurrent cisplatin chemotherapy with postoperative EF-IMRT was safe and well tolerated. The acute and late toxicities are acceptable. The locoregional control rates are hopeful, although distant metastases continue to be the primary mode of failure. Postoperative EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition.

[Differences of blood plasma renin activity, angiotensin II and aldosterone levels in essential or secondary hypertension].

OBJECTIVE: To study on the difference of plasma renin activity (PRA), angiotensin II (Ang II), and aldosterone levels in patients with essential hypertension (EH) or primary aldosteronism (PA) or pheochromocytoma (PHEO), and to analyze the sensitivity and specificity on the diagnosis of PA among patients with hypertension with aldosterone/PRA ratio (ARR). METHODS: The plasma aldosterone, Ang II and PRA concentrations in supine and upright positions were measured by radioimmunoassay from 413 patients including idiopathic hyperaldosteronism (IHA, n = 111), aldosterone-producing adenoma (APA, n = 118), PHEO (n = 98) and EH (n = 86). ARR was calculated. RESULTS: Plasma aldosterone concentrations in both of supine and upright positions in PHEO group [374 (294, 465) pmol/L and 629 (449, 997) pmol/L] and PA group [471 (346, 632) pmol/L and 673 (499, 825) pmol/L] were higher than those in EH group [277 (224, 332) pmol/L and 427 (341, 501) pmol/L] (P < 0.01). They were also higher in APA group [576 (416, 731) pmol/L and 726 (554, 906) pmol/L] than those in IHA group [399 (313, 504) pmol/L and 609 (485, 776) pmol/L] (P < 0.01). Ang II levels in both positions were lower in PA group [43.2 (26.4, 74.4) ng/L and 60.1 (38.5, 103.6) ng/L] than in EH group [56.7 (43.3, 78.9) ng/L and 84.3 (61.3, 108.4) ng/L] or PHEO group [54.3 (29.9, 101.5) ng/L and 102.8 (49.9, 167.0) ng/L] (all P values < 0.01), and there was no difference between IHA and APA group (P > 0.05). The PRA level in both positions of each group were PHEO group [0.3 (0.2, 1.0) µg · L(-1) · h(-1) and 1.4 (0.6, 3.4) µg · L(-1) · h(-1)] > EH group [0.2 (0.1, 0.4) µg · L(-1) · h(-1) and 0.6 (0.4, 1.0) µg · L(-1) · h(-1)] (P < 0.01) > PA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (P < 0.01), and APA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.1 (0.1, 0.3) µg · L(-1) · h(-1)] < IHA group [0.1 (0.1, 0.2) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (supine P < 0.01; upright P < 0.05). APA was divided into 2 types with renin-Ang II-responsive APA (n = 26) and unresponsive APA (n = 92). The plasma aldosterone concentration was lower in supine position but higher in upright position in renin-Ang II-responsive APA than in unresponsive APA patients. ARR in upright was higher in PA group (P < 0.01) but lower in PHEO group (P < 0.05) compared with EH. ARR was higher in APA than in IHA (P < 0.01). The sensitivity and specificity of ARR as 40 (aldosterone unit: ng/dl; PRA unit: µg · L(-1) · h(-1); its value should multiply 27.7 when transferred to pmol/L, simili) were 93% and 76%, respectively. CONCLUSION: The levels of PRA, Ang II and aldosterone from patients with EH, PA and PHEO are significant different. ARR as 40 in upright position could be used for PA screening cutoff point.

Adipocytokines and breast cancer risk.

BACKGROUND: Many researches suggested that obesity increased the risk of breast cancer, but the mechanism was currently unknown. Adipocytokines might mediate the relationship. Our study was aimed to investigate the relationship between serum levels of resistin, adiponectin and leptin and the onset, invasion and metastasis of breast cancer. METHODS: Blood samples were collected from 80 newly diagnosed, histologically confirmed breast cancer patients and 50 age-matched healthy controls. Serum levels of resistin, adiponectin and leptin were determined by enzyme-linked immunosorbent assays (ELISA); fasting blood glucose (FBG), lipids, body mass index (BMI), and waist circumference (WC) were assayed simultaneously. RESULTS: Serum levels of adiponectin ((8.60 +/- 2.92) mg/L vs (10.37 +/- 2.81) mg/L, P = 0.001) and HDL-c were significantly decreased in breast cancer patients in comparison to controls. Serum levels of resistin ((26.35 +/- 5.36) microg/L vs (23.32 +/- 4.75) microg/L, P = 0.000), leptin ((1.35 +/- 0.42) microg/L vs (1.06 +/- 0.39) microg/L, P = 0.003), FBG and triglyceride (TG) in breast cancer patients were increased in contrast to controls, respectively. However, we did not find the significant difference of the serum levels of resistin, adiponectin and leptin between premenopausal breast cancer patients and healthy controls (P = 0.091, 0.109 and 0.084, respectively). The serum levels of resistin, adiponectin and leptin were significantly different between patients with lymph node metastasis (LNM) and those without LNM (P = 0.001, 0.000 and 0.006, respectively). The stepwise regression analysis indicated that the tumor size had the close correlation with leptin (R(2) = 0.414, P = 0.000) and FBG (R(2) = 0.602, P = 0.000). Logistic regression analysis showed that reduced serum levels of adiponectin (OR: 0.805; 95% CI: 0.704 - 0.921; P = 0.001), HDL (OR: 0.087; 95% CI: 0.011 - 0.691, P = 0.021), elevated leptin (OR: 2.235; 95% CI: 1.898 - 4.526; P = 0.004) and resistin (OR: 1.335; 95% CI: 1.114 - 2.354; P = 0.012) increased the risk for breast cancer; Reduced serum levels of adiponectin (OR: 0.742; 95% CI: 0.504 - 0.921; P = 0.003) and elevated leptin (OR: 2.134; 95% CI: 1.725 - 3.921; P = 0.001) were associated with lymph node metastasis of breast cancer. CONCLUSIONS: The decreased serum adiponectin levels and increased serum resistin and leptin levels are risk factors of breast cancer. The low serum adiponectin levels and high serum leptin levels are independent risk factors for metastasis of cancer. The association between obesity and breast cancer risk might be explained by adipocytokines.