Racial Differences in Blood Lipids Lead to Underestimation of Cardiovascular Risk in Black Women in a Nested observational Study.

BACKGROUND: During screening for enrollment in a clinical trial, we noticed potential racial disparities in metabolic syndrome variables in women who responded to our study advertisement. We designed a nested observational study to investigate whether metabolic syndrome variables differed between non-Hispanic blacks and non-Hispanic whites. METHODS: The cohort comprised of women who have met the preliminary clinical trial criteria (body mass index [BMI] 25-45, age 20-75 years, and no use of lipid-lowering medications or supplements). These women, including 116 blacks and 138 whites, provided fasting blood samples for analysis of serum lipid profile. RESULTS: Blacks had lower mean triglycerides (81.1 ± 3.3 mg/dL vs 140.6 ± 5.9 mg/dL; P < .0001), total cholesterol (176.1 ± 3.6 mg/dL vs 201.6 ± 3.3 mg/dL; P < .0001), and low-density lipoprotein (111.7 ± 3.3 mg/dL vs 128.2 ± 2.9 mg/dL; P < .001) and higher mean BMI (37.2 ± 0.5 vs 35.2 ± 0.5; P < .01) and diastolic blood pressure (82.4 ± 0.8 mmHg vs 79.4 ± 0.7 mmHg; P < .01) than whites. Only 7% of blacks, compared with 41% of whites, had triglycerides ≥150 mg/dL; as a result, fewer black women met metabolic syndrome criteria than white women. Additionally, in women with waist circumference ≥88 cm (N = 215), high-density lipoprotein was higher in blacks than in whites (48.3 ± 1.5 mg/dL vs 44.2 ±1.3 mg/dL; P < .05). CONCLUSIONS: Due to racial differences in blood lipids, current metabolic syndrome criteria may result in underestimation of cardiovascular risk in blacks.

Phase II study of long-term androgen suppression with bevacizumab and intensity-modulated radiation therapy (IMRT) in high-risk prostate cancer.

PURPOSE: We report a Phase II trial assessing the acute and late toxicities of intensity-modulated radiation therapy (IMRT), long-term androgen suppression (LTAS), and bevacizumab in patients with high-risk localized prostate cancer. METHODS AND MATERIALS: We treated 18 patients with LTAS with bicalutamide and goserelin in combination with bevacizumab and IMRT. Bevacizumab (10 mg/kg every 2 weeks) was administered for the first 16 weeks, and 15 mg/kg was then given every 3 weeks for 12 additional weeks, with an IMRT dose of 77.9 Gy to the prostate, 64.6 Gy to the seminal vesicles, and 57 Gy to the pelvic lymph nodes. Patients were eligible if they had clinical stage T2b to T4, a Gleason sum score of 8 to 10, or a prostate- specific antigen level of 20ng/mL or greater. The primary endpoint of the study was evaluation of acute and late toxicities. RESULTS: The median age was 69 years, with a median pretreatment prostate-specific antigen level of 12.5 ng/mL and Gleason score of 8. The pretreatment clinical stage was T1c in 4 patients, T2 in 11, and T3 in 3. All patients completed IMRT with median follow-up of 34 months (range, 28-40 months) The most common Grade 2 or higher toxicities were hypertension (61% of patients with Grade 2 and 11% with Grade 3), proteinuria (28% with Grade 2 and 6% with Grade 3), and leucopenia (28% with Grade 2). No Grade 4 or higher acute toxicities were reported. Late toxicities included proctitis (6% of patients with Grade 2 and 11% with Grade 3), rectal bleeding (6% with Grade 2 and 11% with Grade 3), hematuria (6% with Grade 2), proteinuria (17% with Grade 2), hyponatremia (6% with Grade 3), cystitis (6% with Grade 3), and urinary retention (6% with Grade 2 and 11% with Grade 3). Grade 4 prostatitis occurred in 1 patient (6%). CONCLUSIONS: Bevacizumab does not appear to exacerbate the acute effects of IMRT. Late toxicities may have been worsened with this regimen. Further investigations of bevacizumab with LTAS and IMRT should be performed cautiously.

A program consisting of a phytonutrient-rich medical food and an elimination diet ameliorated fibromyalgia symptoms and promoted toxic-element detoxification in a pilot trial.

BACKGROUND: An effective treatment for fibromyalgia (FM) has yet to become available. OBJECTIVE: To assess the efficacy ofa lifestyle program consisting of a modified elimination diet and a supplemental medical food on clinical symptoms of FM assessed by the Fibromyalgia Impact Questionnaire (FIQ), FibroQuest Symptoms Survey (FibroQuest), Medical Symptoms Questionnaire (MSQ), metallothionein mRNA expression, and urinary toxic element excretion. METHODS: Eight women (aged 48-74 years) were enrolled in an 8-week pilot trial employing a sequential design. During the initial 4-week Program A (control), participants consumed a modified US Department of Agriculture food pyramid diet and a rice protein powder supplement that provided basic macronutrient support. During the second 4-week Program B (intervention), participants consumed a modified elimination diet and a phytonutrient-rich medical food. RESULTS: Compared to baseline, both programs showed trends toward lower mean FIQ total score, MSQ total score, and FibroQuest total score, FIQ stiffness score, and FibroQuest headaches score. Compared to Program A, Program B resulted in a significant decrease (P< .05) in the FIQpain score and stiffness score. Participants also had better pain tolerance at five tender points during Program B than during Program A. Higher metallothionein mRNA expression was observed during Program B. An increase in creatinine-adjusted mercury excretion and suggestive increase in creatinine-adjusted arsenic excretion were noted when Program B was compared to baseline. Urinary mercury/arsenic concentrations were inversely associated with FIQand FibroQuest scores. CONCLUSIONS: Program B was shown to be a safe and efficacious botanically derived medical food treatment program for the amelioration of FM symptoms.

Nutritional supplementation of hop rho iso-alpha acids, berberine, vitamin D3, and vitamin K1 produces a favorable bone biomarker profile supporting healthy bone metabolism in postmenopausal women with metabolic syndrome.

Metabolic syndrome poses additional risk for postmenopausal women who are already at risk for osteoporosis. We hypothesized that a nutritional supplement containing anti-inflammatory phytochemicals and essential bone nutrients would produce a favorable bone biomarker profile in postmenopausal women with metabolic syndrome. In this 14-week, randomized trial, 51 women were instructed to consume a modified Mediterranean-style, low-glycemic-load diet and to engage in aerobic exercise. Those in the intervention arm (n = 25) additionally received 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D3, and 500 µg vitamin K1 twice daily. Forty-five women completed the study. Baseline nutrient intake did not differ between arms. Compared with baseline, the intervention arm exhibited an approximate 25% mean decrease (P < .001) in serum osteocalcin (indicative of bone turnover), whereas the placebo arm exhibited a 21% increase (P = .003). Serum 25-hydroxyvitamin D increased 23% (P = .001) in the intervention arm and decreased 12% (P = .03) in the placebo arm. The between-arm differences for osteocalcin and 25-hydroxyvitamin D were statistically significant. Serum insulin-like growth factor I was statistically increased in both arms, but the between-arm differences were not statistically significant. Subanalysis showed that among those in the highest tertile of baseline insulin-like growth factor I, the intervention arm exhibited a significant increase in amino-terminal propeptide of type I collagen, whereas the placebo arm showed a significant decrease at 14 weeks. Treatment with rho iso-alpha acids, berberine, vitamin D3, and vitamin K1 produced a more favorable bone biomarker profile indicative of healthy bone metabolism in postmenopausal women with metabolic syndrome.

Subjects with elevated LDL cholesterol and metabolic syndrome benefit from supplementation with soy protein, phytosterols, hops rho iso-alpha acids, and Acacia nilotica proanthocyanidins.

BACKGROUND: Metabolic syndrome is associated with increased cardiovascular disease (CVD) risk, a risk that is significantly increased when accompanied by elevated low-density lipoprotein cholesterol (LDL-C). Whereas lifestyle therapies are the initial intervention of choice for both of these risk factors, it has not been clearly determined that this approach is efficacious when they occur concomitantly. OBJECTIVE: To evaluate effects of supplementing a lifestyle program with a medical food and nutraceutical in individuals with metabolic syndrome and elevated LDL-C. METHODS: We conducted a subgroup analysis of a 12-week, randomized trial in adults with metabolic syndrome; data from those with LDL-C ≥ 160 mg/dL were analyzed. Control-arm subjects were instructed to consume a modified Mediterranean-style, low-glycemic-load diet (MED, n = 12). Treatment-arm subjects received a phytochemical-enhanced diet (PED, n = 12) consisting of the same low-glycemic-load diet plus a medical food containing soy protein and plant sterols and a nutraceutical containing hops rho iso-alpha acids and acacia proanthocyanidins. All subjects received identical aerobic exercise counseling. RESULTS: At 12 weeks, mean weight loss did not differ between arms. However, the PED arm exhibited greater improvement than the MED arm (P < .05) in total cholesterol, LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), cholesterol/HDL-C, triglyceride/HDL-C, apolipoprotein (apo) B, apo B/apo A-1, homocysteine, total LDL particle number, and large HDL particle number. All individuals in the PED arm but only one third in the MED arm achieved LDL-C levels < 160 mg/dL. CONCLUSION: Individuals at high CVD risk benefit from a soy/phytosterol containing medical food and phytochemical supplemented lifestyle program.

Hop rho iso-alpha acids, berberine, vitamin D3 and vitamin K1 favorably impact biomarkers of bone turnover in postmenopausal women in a 14-week trial.

Osteoporosis is a major health issue facing postmenopausal women. Increased production of pro-inflammatory cytokines resulting from declining estrogen leads to increased bone resorption. Nutrition can have a positive impact on osteoporosis prevention and amelioration. The objective of this study was to investigate the impact of targeted phytochemicals and nutrients essential for bone health on bone turnover markers in healthy postmenopausal women. In this 14-week, single-blinded, 2-arm placebo-controlled pilot study, all women were instructed to consume a modified Mediterranean-style low-glycemic-load diet and to engage in limited aerobic exercise; 17 randomized to the placebo and 16 to the treatment arm (receiving 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D(3) and 500 microg vitamin K(1), twice daily). Thirty-two women completed the study. Baseline nutrient intake did not differ between arms. At 14 weeks, the treatment arm exhibited an estimated 31% mean reduction (P = 0.02) in serum osteocalcin (a marker of bone turnover), whereas the placebo arm exhibited a 19% increase (P = 0.03) compared to baseline. Serum 25-hydroxyvitamin D (25(OH)D) increased by 13% (P = 0.24) in the treatment arm and decreased by 25% (P < 0.01) in the placebo arm. The between-arm differences for OC and 25(OH)D were statistically significant. Serum IGF-I was increased in both arms, but the increase was more significant in the treatment arm at 14 weeks (P < 0.01). Treatment with hop rho iso-alpha acids, berberine sulfate trihydrate, vitamin D(3) and vitamin K(1) produced a more favorable bone biomarker profile that supports a healthy bone metabolism.

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.

A Javascript library that uses Windows Script Host (WSH) to analyze prostate motion data fragmented across a multitude of Excel files by the Calypso 4D Localization System.

The Calypso 4D Localization System records prostate motion continuously during radiation treatment. It stores the data across thousands of Excel files. We developed Javascript (JScript) libraries for Windows Script Host (WSH) that use ActiveX Data Objects, OLE Automation and SQL to statistically analyze the data and display the results as a comprehensible Excel table. We then leveraged these libraries in other research to perform vector math on data spread across multiple access databases.

Adiponectin and resistin are associated with risk for myelodysplastic syndrome, independently from the insulin-like growth factor-I (IGF-I) system.

AIM: Obesity has been implicated in the aetiology of myelogenous leukaemia and myelodysplasia (MDS). We hypothesised that altered secretion of adiponectin and resistin may underlie this association. We thus investigated the role of both total and high molecular weight (HMW) adiponectin and resistin in MDS. METHODS: In a case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender and age between 2004 and 2007. Total and HMW adiponectin, resistin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein (IGFBP-3) were determined. RESULTS: Lower serum total or HMW adiponectin and/or resistin levels were independently associated with higher risk of MDS controlling for age, gender, BMI and serum levels of leptin, IGF-I and IGFBP-3 (p<0.002). Although total and HMW adiponectin were both significantly inversely associated with MDS when modelled either in quartiles or continuously, HMW did not offer any substantial additional predictive value over total adiponectin (Odds ratio (OR)=0.91 versus 0.93 for a 1 microg/ml change, respectively). IGF-I was positively associated with MDS by bivariate analysis and both IGF-I and IGFBP-3 were higher in advanced MDS and higher risk stages, but were not significantly and independently associated with MDS. CONCLUSION: Total and HMW adiponectin may have a protective role in MDS, whereas resistin levels may be decreased via a compensatory mechanism.

Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk.

Breast cancer risk is higher among obese women and women with diabetes. Adiponectin is a protein exclusively secreted by adipose tissue, circulating levels of which have been associated with breast cancer risk. Whether genetic variants within the adiponectin pathway are associated with breast cancer risk is unknown. To explore the association of genetic variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with breast cancer risk, we conducted a case control study of female patients with breast cancer and healthy female controls from New York City recruited between 1999 and 2004. We genotyped 733 hospital-based breast cancer cases and 839 controls for 10 haplotype-tagging single nucleotide polymorphisms (SNP) of ADIPOQ and ADIPOR1. Two ADIPOQ SNPs (rs2241766 and rs1501299), which have been associated with circulating levels of adiponectin, were associated with breast cancer risk [rs1501299*GG: odd ratios (OR), 1.80; 95% confidence interval (95% CI), 1.14-2.85; rs2241766*TG: OR, 0.61; 95% CI, 0.46-0.80]. One ADIPOR1 SNP (rs7539542), which modulates expression of adiponectin receptor 1 mRNA, was also associated with breast cancer risk (OR, 0.51; 95% CI, 0.28-0.92). Based on the known function of rs2241766 and rs1501299, we categorized individuals by adiponectin signaling status and found that, when compared with high signalers, intermediate signalers had a 4.16-fold increase in breast cancer risk (95% CI, 0.49-35.19), and low signalers had a 6.56-fold increase in breast cancer risk (95% CI, 0.78-54.89; P(trend) = 0.001). This is the first report of an association between functionally relevant variants of the adiponectin pathway and breast cancer risk. The results warrant further studies of the adiponectin pathway in breast cancer.

Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors.

Circulating adiponectin is inversely associated with colorectal carcinoma. However, adiponectin receptor expression has not been examined in normal gastrointestinal tissue, colorectal malignancies, or gastrointestinal stromal tumors (GISTs). We collected 40 colorectal carcinomas and 12 non-tumor colorectal tissue specimens from patients with colorectal cancer, as well as 45 tumor and 13 non-tumor specimens from patients with GIST. Expression and localization of adiponectin receptors (AdipoR1 and AdipoR2) were assessed using immunohistochemistry. We also confirmed expression of adiponectin receptors using rtPCR in matched normal and colorectal cancer specimens obtained from five patients. Finally, we detected adiponectin receptors and assessed adiponectin signaling in three colon cancer cell lines. Adiponectin receptor expression, assessed by either rtPCR or immunohistochemistry, was present in normal tissue and was significantly lower than in colorectal carcinomas. Among carcinomas, 95% displayed positive or strongly positive expression of AdipoR1 and 88% of AdipoR2, versus 8% and 0%, respectively, for non-tumor specimens (P<0.0001). AdipoR1 expression assessed by rtPCR was 1.6-fold higher in tumor than in non-tumor tissue (P<0.05). In addition, we found that adiponectin at physiological concentrations can activate in vitro intracellular signaling pathways in three colon cancer cell lines, expressing both adiponectin receptors 1 and 2. No significant differences in expression of adiponectin receptors in tumor versus non-tumor GI specimens were detected among patients with GIST. Colon cancer cell lines express adiponectin receptors, through which adiponectin activates in vitro intracellular signaling pathways. Adiponectin receptors are also detected in normal GI tissue and their expression is elevated in colorectal carcinomas, but not in GIST.

Gene expression of adiponectin receptors in human visceral and subcutaneous adipose tissue is related to insulin resistance and metabolic parameters and is altered in response to physical training.

OBJECTIVE: Adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2, respectively) mediate the effects of adiponectin on glucose and lipid metabolism in vivo. We examined whether AdipoR1 and/or AdipoR2 mRNA expression in human adipose tissue is fat-depot specific. We also studied whether their expression in visceral and subcutaneous fat depots is associated with metabolic parameters and whether their expression is regulated by intensive physical exercise. RESEARCH DESIGN AND METHODS: We determined metabolic parameters and assessed AdipoR1 and AdipoR2 mRNA expression using quantitative real-time PCR in adipose tissue in an observational study of 153 subjects and an interventional study of 60 subjects (20 each with normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes) before and after intensive physical training for 4 weeks. RESULTS: AdipoR1 and AdipoR2 mRNA expression is not significantly different between omental and subcutaneous fat, but their expression is several-fold lower in adipose tissue than in muscle. AdipoR2 mRNA expression in visceral fat is highly correlated with its expression in subcutaneous fat. AdipoR2 mRNA expression in both visceral and subcutaneous fat is positively associated with circulating adiponectin and HDL levels but negatively associated with obesity as well as parameters of insulin resistance, glycemia, and other lipid levels before and after adjustment for fat mass. Physical training for 4 weeks resulted in increased AdipoR1 and AdipoR2 mRNA expression in subcutaneous fat. CONCLUSIONS: AdipoR2 mRNA expression in fat is negatively associated with insulin resistance and metabolic parameters independently of obesity and may mediate the improvement of insulin resistance in response to exercise.

Esophagectomy--it's not just about mortality anymore: standardized perioperative clinical pathways improve outcomes in patients with esophageal cancer.

BACKGROUND: Esophageal resection (ER) remains the standard therapy for early esophageal cancer; however, because of concerns regarding high levels of morbidity and mortality reported in analyses of national databases, many patients are relegated to less effective endoscopic or chemotherapeutic approaches. METHODS: All patients undergoing esophagectomy by a single surgeon for cancer or high-grade dysplasia between 05/91-05/06 were prospectively entered into an IRB-approved database. All aspects of work-up and treatment were guided by an evolving standardized perioperative clinical pathway. RESULTS: Three hundred forty consecutive patients, mean age of 64 (33-90), underwent ER for Barrett's esophagus (17) or invasive cancer stages I-87, II-133, III-94, IV-9. One hundred thirty-nine (41%) had neoadjuvant therapy. Sixty-three percent were American Society of Anesthesiologists class III or IV, and five different operative approaches were used. Patient were managed intraoperatively with a "fluid restriction" protocol. Mean intraoperative blood loss was 230 cc. 99.5% of patients were extubated immediately, and mean ICU and hospital stays were 2.25 (1-30) and 11.5 (6-49) days, respectively. Postoperative analgesia was managed with patient-controlled epidural analgesia in 98.5%, and 86% were mobilized on day 1 after surgery. Complications occurred in 153 patients (45%), most commonly atrial dysrhythmia (13%), and postoperative delirium (11%). Anastomotic leaks occurred in 13 patients (3.8%). Mortality occurred in one patient (0.3%). No significant differences were seen in length of stay, operative time, blood loss, or complications in patients receiving neoadjuvant therapy. For stages I, II, and III, patients between 1998-2004 Kaplan-Meier 5-year cumulative survival was 92.4, 57.1, and 34.5%, respectively. CONCLUSIONS: Surgical treatment of esophageal cancer can be done with moderate morbidity and very low mortality, and the expectation of improved levels of survival, especially in early-stage patients. Standardized perioperative clinical pathways can provide the infrastructure for the treatment of these patients and should include increased efforts to minimize blood loss and transfusions, improve postoperative pain control and extubation rates, and facilitate early mobilization and discharge. ER, as sole therapy or in combination with radiation/chemotherapy, should remain the standard of care in patients with early and locoregional esophageal cancer.

Circulating adiponectin levels and expression of adiponectin receptors in relation to lung cancer: two case-control studies.

BACKGROUND: Decreased circulating levels of adiponectin, an adipocyte-secreted hormone and endogenous insulin sensitizer, have been associated with several obesity-related malignancies. Thiazolidinedione administration, which increases adiponectin levels, decreases risk for lung cancer. Whether circulating adiponectin levels are associated with lung cancer and/or whether adiponectin receptors are expressed in lung cancer remains unknown. METHODS: We conducted a case-control study of 85 patients with incidental, histologically confirmed lung cancer and 170 healthy controls matched by gender and age. In a separate study, archival lung specimens from 134 cancerous and 8 noncancerous tissues were examined for relative expression of adiponectin receptors AdipoR1 and AdipoR2 using immunohistochemistry. RESULTS: Tobacco smoking, heavy alcohol intake and education were all associated with lung cancer risk, whereas serum adiponectin levels were not significantly different between cases and controls (multiple logistic regression, odds ratio per SD of adiponectin among controls: 1.13, 95% confidence interval: 0.64-2.02). Adiponectin levels were significantly lower (odds ratio: 0.25, 95% confidence interval: 0.10-0.78) among patients with advanced compared to those with limited disease stage. Expression of adiponectin receptors was apparent only in the cancerous lung tissue (64.2% AdipoR1 and 61.9% AdipoR2 in cancerous vs. 0% among noncancerous tissue). Specifically, AdipoR1 was expressed in all disease types, but no difference was noted with disease stage, whereas AdipoR2 was mainly expressed in the non-small cell carcinomas and more prominently in the advanced disease stage (80%). CONCLUSIONS: Circulating adiponectin levels are not different in cases of this malignancy - which seems to be unrelated to obesity and insulin resistance - compared to their healthy controls, though hormonal levels were significantly lower in advanced versus limited lung cancer. Both adiponectin receptors were expressed in cancerous lung tissue, but not in normal control tissue and there was a differential expression by disease stage. These findings should be further explored, especially in the context of the recently reported protective effect of thiazolidinediones in diabetic patients with lung cancer.

Circulating adiponectin and leptin in relation to myelodysplastic syndrome: a case-control study.

OBJECTIVE: Adiponectin plays a protective role in several malignancies, including myeloblastic leukemia, whereas leptin may increase the proliferation of progenitor cells and may stimulate leukemic cell growth in vitro. We investigated the role of adiponectin and leptin levels in the etiopathogenesis of myelodysplastic syndromes (MDS), a preleukemic condition with increasing incidence which has recently been associated with obesity. METHODS: In a case-control study, 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender and age were studied between 2004 and 2007, and blood samples were collected. RESULTS: Higher serum adiponectin levels were associated with lower risk of MDS by bivariate analysis and after adjusting for age, gender, body mass index and serum levels of leptin (p < 0.001). Subjects in the third quartile for leptin levels had a lower risk of MDS than controls, and low leptin concentrations were observed in low-risk MDS patients with normal or good prognostic karyotype after adjusting for age, gender and body mass index. CONCLUSIONS: Circulating adiponectin and leptin may play an important role in MDS etiopathogenesis. Future studies are needed to confirm these associations and to explore underlying mechanisms.

Sugarcane ShSUT1: analysis of sucrose transport activity and inhibition by sucralose.

Plant sucrose transporters (SUTs) are members of the glycoside-pentoside-hexuronide (GPH) cation symporter family (TC2.A.2) that is part of the major facilitator superfamily (MFS). All plant SUTs characterized to date function as proton-coupled symporters and catalyze the cellular uptake of sucrose. SUTs are involved in loading sucrose into the phloem and sink tissues, such as seeds, roots and flowers. Because monocots are agriculturally important, SUTs from cereals have been the focus of recent research. Here we present a functional analysis of the SUT ShSUT1 from sugarcane, an important crop species grown for its ability to accumulate high amounts of sucrose in the stem. ShSUT1 was previously shown to be expressed in maturing stems and plays an important role in the accumulation of sucrose in this tissue. Using two-electrode voltage clamping in Xenopus oocytes expressing ShSUT1, we found that ShSUT1 is highly selective for sucrose, but has a relatively low affinity for sucrose (K(0.5) = 8.26 mM at pH 5.6 and a membrane potential of -137 mV). We also found that the sucrose analog sucralose (4,1',6'-trichloro-4,1',6'-trideoxy-galacto-sucrose) is a competitive inhibitor of ShSUT1 with an inhibition coefficient (K(i)) of 16.5 mM. The presented data contribute to our understanding of sucrose transport in plants in general and in monocots in particular.

An integrated approach to measuring tumor oxygen status using human melanoma xenografts as a model.

Tumor oxygen status is a reliable prognostic marker that impacts malignant progression and outcome of tumor therapy. However, tumor oxygenation is heterogeneous and cannot be sufficiently described by a single parameter. It is influenced by several factors including microvessel density (MVD), blood flow (BF), blood volume (BV), blood oxygen saturation, tissue pO(2), oxygen consumption rate, and hypoxic fraction. The goal of this investigation was to integrate these measurements to obtain a comprehensive profile of tumor oxygenation. Platelet/endothelial cell adhesion molecule immunohistochemistry, the recessed oxygen microelectrode, color and power Doppler ultrasound (DUS), and diffuse light spectroscopy (DLS) were used to measure tumor oxygen status using vascular endothelial growth factor (VEGF)-transfected hypervascular human melanoma xenografts and their nontransfected counterparts as a model. NIH1286 human melanoma cells were transfected with a retroviral vector +/- a 720-bp fragment of human VEGF(121). High VEGF-producing clones were selected by ELISA. Oxygen consumption rate was measured in NIH1286/VEGF+ [VEGF-transfected cells (VEGF+ cells)] and NIH1286/Vec cells [cells transfected with vector alone (Vec cells)] using a standard Clark oxygen electrode. Athymic nude 6-8-week-old mice received s.c. injection in the right flank with 5 x 10(6) VEGF+ or Vec cells. When tumors were 10-14 mm in maximum dimension, serum was analyzed for VEGF by ELISA. Cryopreserved tumor tissue sections were immunostained for platelet/endothelial cell adhesion molecule, and MVD measurements were made. Tumor-bearing mice were anesthetized, and pO(2) measurements were made using Eppendorf pO(2) histograph or the recessed oxygen microelectrode. Tumor BF and BV were measured by quantitative analysis of DUS images. DLS was used to measure tumor BF and blood oxygen saturation variation. VEGF+ cell supernatants had 15,500 pg/ml VEGF, and Vec cells had 10 pg/ml. VEGF+ and Vec cells had equivalent oxygen consumption rates. VEGF+ tumors had a faster growth rate than Vec tumors. Serum from VEGF+ tumor-bearing mice showed 4,211 pg/ml VEGF, whereas VEGF was undetectable in the serum of control mice. MVD values were 74 +/- 11 in VEGF+ tumors and 39 +/- 4 in control tumors at x200 magnification/0.95-mm(2) area. The median pO(2) values were 3.5-fold higher in VEGF+ tumors than in Vec tumors by the recessed oxygen microelectrode and 18-fold higher by Eppendorf pO(2) histograph. DUS showed a 3.3-fold higher mean BF and a 5.5-fold higher BV in VEGF+ tumors than in Vec tumors. DLS showed a 3.2-fold higher mean BF and 1.7-fold higher oxygen saturation in the hypervascular tumors as compared with the control tumor type, consistent with increased BF and BV data by DUS. An integrated approach that yields a comprehensive and consistent profile of oxygen status in tumors could potentially provide critical information for prognosis and treatment.