Nutrition and Cancer-an International Journal, 1999
... William J. Aronson, Christopher N. Tymchuk, Robert M. Elashoff, William H. McBride, Colin McL... more ... William J. Aronson, Christopher N. Tymchuk, Robert M. Elashoff, William H. McBride, Colin McLean, Hejing Wang, and David Heber ... Page 3. fresh food. Each time the mice received fresh food, the calo-ric intake from the prior feeding period was determined. ...
The short term addition of nandrolone decanoate to combination chemotherapy given to patients wit... more The short term addition of nandrolone decanoate to combination chemotherapy given to patients with unresectable non-small cell lung cancer was evaluated in a randomized, prospective trial. Patients were treated with doxorubicin 50 mg/M2 intravenously, cyclophosphamide 300 mg/M2 intravenously, CCNU 50 mg/M2 orally, vincristine 1.4 mg/M2 intravenously, with and without cisplatin 50 mg/M2 intravenously, all given every 28 days. In addition, patients were randomized to receive either nandrolone decanoate 200 mg intramuscularly weekly for 4 weeks or no additional therapy. Patient age, disease extent, performance score, and pretreatment weight loss were similar in the two treatment arms. Objective antitumor response frequency was comparable on both treatment arms with median survival somewhat longer for patients receiving the androgen (median survival 5.5 months without and 8.2 months with nandrolone decanoate). There was a trend for less severe weight loss on the nandrolone decanoate arm (average weight loss 0.8 +/- 0.15 kg versus 0.21 +/- 0.18 kg, respectively), with half as many patients experiencing weight loss on nandrolone decanoate (25% versus 12%). A separate concurrent study has demonstrated decreased free testosterone levels in 66% of patients with advanced cancer studied prior to chemotherapy treatment, therefore, further prospective studies in which pretreatment testosterone levels are used to guide androgen administration are needed to define more precisely a role for androgen replacement therapy in non-small cell lung cancer.
For the first time in human history, the numbers of overweight and underweight individuals are ab... more For the first time in human history, the numbers of overweight and underweight individuals are about the same, at 2.1 billion each. Along with the current worldwide obesity epidemic is the explosion of obesity- and overweight-related health problems, including diabetes and the metabolic syndrome, musculoskeletal disorders,cardiovascular disease, pulmonary disorders, and certain forms of cancer. Obesity and overweight account for a significant percentage of overall health care costs and contribute significantly to morbidity and mortality in the United States and around the world.
Berry fruits are widely consumed in our diet and have attracted much attention due to their poten... more Berry fruits are widely consumed in our diet and have attracted much attention due to their potential human health benefits. Berries contain a diverse range of phytochemicals with biological properties such as antioxidant, anticancer, anti-neurodegerative, and anti-inflammatory activities. In the current study, extracts of six popularly consumed berries--blackberry, black raspberry, blueberry, cranberry, red raspberry and strawberry--were evaluated for their phenolic constituents using high performance liquid chromatography with ultraviolet (HPLC-UV) and electrospray ionization mass spectrometry (LC-ESI-MS) detection. The major classes of berry phenolics were anthocyanins, flavonols, flavanols, ellagitannins, gallotannins, proanthocyanidins, and phenolic acids. The berry extracts were evaluated for their ability to inhibit the growth of human oral (KB, CAL-27), breast (MCF-7), colon (HT-29, HCT116), and prostate (LNCaP) tumor cell lines at concentrations ranging from 25 to 200 micro g/mL. With increasing concentration of berry extract, increasing inhibition of cell proliferation in all of the cell lines were observed, with different degrees of potency between cell lines. The berry extracts were also evaluated for their ability to stimulate apoptosis of the COX-2 expressing colon cancer cell line, HT-29. Black raspberry and strawberry extracts showed the most significant pro-apoptotic effects against this cell line. The data provided by the current study and from other laboratories warrants further investigation into the chemopreventive and chemotherapeutic effects of berries using in vivo models.
Most primary care physicians do not treat obesity, citing lack of time, resources, insurance reim... more Most primary care physicians do not treat obesity, citing lack of time, resources, insurance reimbursement, and knowledge of effective interventions as significant barriers. To address this need, a 10-minute intervention delivered by the primary care physician was coupled with individual dietary counseling sessions delivered by a registered dietitian via telephone with an automated calling system (House-Calls, Mobile, AL). Patients were seen for follow-up by their physician at weeks 4, 12, 24, 36 and 52. A total of 252 patients (202 women and 50 men) were referred by 18 primary care physicians to the program. The comorbid conditions reported for all patients at baseline included low back pain, 29% (n = 72); hypertension, 45% (n = 113); hypercholesterolemia, 41% (n = 104); type 2 diabetes, 10% (n = 26); and sleep apnea, 5% (n = 12). When offered a choice of meal plans based on foods or meal replacements, two-thirds of patients (n = 166) chose to use meal replacements (Ultra Slim-Fast; Slim-Fast Foods Co., West Palm Beach, FL) at least once daily. Baseline weights of subjects averaged 200 ± 46 lb for women (n = 202) and 237 ± 45 lb for men (n = 50). Patients completing 6 months in the program lost an average of 19.0 ± 4.0 lb for women (n = 94) and 15.5 ± 8.2 lb for men (n = 26). Physicians reported a high degree of satisfaction with the program, suggesting that a brief, effective physician-directed program with nutritionist support by telephone can be implemented in a busy primary care office.
Phytochemicals from fruits such as the pomegranate (Punica granatum L) may inhibit cancer cell pr... more Phytochemicals from fruits such as the pomegranate (Punica granatum L) may inhibit cancer cell proliferation and apoptosis through the modulation of cellular transcription factors and signaling proteins. In previous studies, pomegranate juice (PJ) and its ellagitannins inhibited proliferation and induced apoptosis in HT-29 colon cancer cells. The present study examined the effects of PJ on inflammatory cell signaling proteins in the HT-29 human colon cancer cell line. At a concentration of 50 mg/L PJ significantly suppressed TNFalpha-induced COX-2 protein expression by 79% (SE = 0.042), total pomegranate tannin extract (TPT) 55% (SE = 0.049), and punicalagin 48% (SE = 0.022). Additionally, PJ reduced phosphorylation of the p65 subunit and binding to the NFkappaB response element 6.4-fold. TPT suppressed NFkappaB binding 10-fold, punicalagin 3.6-fold, whereas ellagic acid (EA) (another pomegranate polyphenol) was ineffective. PJ also abolished TNFalpha-induced AKT activation, needed for NFkappaB activity. Therefore, the polyphenolic phytochemicals in the pomegranate can play an important role in the modulation of inflammatory cell signaling in colon cancer cells.
Phytoestrogens may function as partial agonists or antagonists of estrogen in many tissues includ... more Phytoestrogens may function as partial agonists or antagonists of estrogen in many tissues including bone. Five phytoestrogens, belonging to the isoflavones and the flavonoids groups, were assayed in the human MG-63 osteoblastic cell line for their ability to stimulate transcriptional activity of an estrogen-response element (ERE)-luciferase reporter gene via the estrogen receptor beta (ERbeta). Although MG-63 cells were shown to express endogenous estrogen receptors, estradiol (E2) did not affect transcriptional activity of an ERE reporter in these cells. However, E2 did activate the ERE-reporter significantly in MG-63 cells where ERbeta was overexpressed. The isoflavones, genistein and daidzein, caused a dose-dependent increase in the ERE-reporter activity in MG-63 cells overexpressing ERbeta. Among the flavonoids, kaempferol activated ERE-reporter activity, whereas puerarin inhibited ERE-reporter transcription in cells overexpressing ERbeta. Quercetin had no effect on ERE-reporter activity over a concentration range of 10(-10)-10(-6) mol/l. The ERE-reporter activity induced by daidzein, genistein, and kaempferol was blocked by both ICI 182780 and 4-hydroxytamoxifen and partly blocked by puerarin. Our results demonstrated that different phytoestrogens exhibited differential transcription activity of an ERE-reporter via ERbeta-mediated mechanisms in MG-63 cells.
Objective: Although weight management is an important component in the treatment of type 2 diabet... more Objective: Although weight management is an important component in the treatment of type 2 diabetes, there has been concern about the use of liquid meal replacements (MRs) in treating obese patients with type 2 diabetes because of the sugar content of the MRs. The goal of this study was to evaluate the safety and feasibility of using MRs for weight loss in obese patients with type 2 diabetes.Research Methods and Procedures: Seventy-five subjects with type 2 diabetes, treated only with oral agents, were recruited for this 12-week clinical study. Subjects were randomized into three groups using either a MR containing lactose, fructose, and sucrose, a MR in which fructose and sucrose were replaced with oligosaccharides (sugar-free Slim-Fast), or an exchange diet plan (EDP) using the proportion of macronutrients recommended by the American Diabetes Association.Results: Fifty-seven patients (41 MR and 16 EDP) finished the study. None developed serious adverse effects, including major hypoglycemic reactions. Weight losses in the MR 1 and MR 2 groups were comparable (6.4% and 6.7%, respectively) and greater than the weight loss in the EDP group (4.9%). Fasting glucose level was significantly reduced in the MR group compared with the EDP group (p = 0.012). There was a significant reduction in the MR group in total cholesterol and low-density lipoprotein cholesterol that was not seen in the EDP group.Discussion: We have shown that liquid MRs are a safe and effective weight loss tool for obese subjects with type 2 diabetes, and can result in improvements in body weight, glucose, insulin, hemoglobin A1c and lipid levels.
Strawberry (Fragaria x ananassa Duch.) fruits contain phenolic compounds that have antioxidant, a... more Strawberry (Fragaria x ananassa Duch.) fruits contain phenolic compounds that have antioxidant, anticancer, antiatherosclerotic and anti-neurodegenerative properties. Identification of food phenolics is necessary since their nature, size, solubility, degree and position of glycosylation and conjugation influence their absorption, distribution, metabolism and excretion in humans. Freeze-dried whole strawberry fruit powder and strawberry fruit extracts were analyzed by liquid chromatography electrospray ionization mass spectrometry (LC–ESI–MS) methods. Phenolics were identified as ellagic acid (EA), EA-glycosides, ellagitannins, gallotannins, anthocyanins, flavonols, flavanols and coumaroyl glycosides. The anthocyanidins were pelargonidin and cyanidin, found predominantly as their glucosides and rutinosides. The major flavonol aglycons were quercetin and kaempferol found as their glucuronides and glucosides. LC–ESI–MS/MS methods differentiated EA from quercetin conjugates since both aglycons have identical molecular weights (302g/mol). The identification of strawberry phenolics is necessary to generate standardized materials for in vitro and in vivo studies and for the authentication of strawberry-based food products.
Nutrition and Cancer-an International Journal, 1999
... William J. Aronson, Christopher N. Tymchuk, Robert M. Elashoff, William H. McBride, Colin McL... more ... William J. Aronson, Christopher N. Tymchuk, Robert M. Elashoff, William H. McBride, Colin McLean, Hejing Wang, and David Heber ... Page 3. fresh food. Each time the mice received fresh food, the calo-ric intake from the prior feeding period was determined. ...
The short term addition of nandrolone decanoate to combination chemotherapy given to patients wit... more The short term addition of nandrolone decanoate to combination chemotherapy given to patients with unresectable non-small cell lung cancer was evaluated in a randomized, prospective trial. Patients were treated with doxorubicin 50 mg/M2 intravenously, cyclophosphamide 300 mg/M2 intravenously, CCNU 50 mg/M2 orally, vincristine 1.4 mg/M2 intravenously, with and without cisplatin 50 mg/M2 intravenously, all given every 28 days. In addition, patients were randomized to receive either nandrolone decanoate 200 mg intramuscularly weekly for 4 weeks or no additional therapy. Patient age, disease extent, performance score, and pretreatment weight loss were similar in the two treatment arms. Objective antitumor response frequency was comparable on both treatment arms with median survival somewhat longer for patients receiving the androgen (median survival 5.5 months without and 8.2 months with nandrolone decanoate). There was a trend for less severe weight loss on the nandrolone decanoate arm (average weight loss 0.8 +/- 0.15 kg versus 0.21 +/- 0.18 kg, respectively), with half as many patients experiencing weight loss on nandrolone decanoate (25% versus 12%). A separate concurrent study has demonstrated decreased free testosterone levels in 66% of patients with advanced cancer studied prior to chemotherapy treatment, therefore, further prospective studies in which pretreatment testosterone levels are used to guide androgen administration are needed to define more precisely a role for androgen replacement therapy in non-small cell lung cancer.
For the first time in human history, the numbers of overweight and underweight individuals are ab... more For the first time in human history, the numbers of overweight and underweight individuals are about the same, at 2.1 billion each. Along with the current worldwide obesity epidemic is the explosion of obesity- and overweight-related health problems, including diabetes and the metabolic syndrome, musculoskeletal disorders,cardiovascular disease, pulmonary disorders, and certain forms of cancer. Obesity and overweight account for a significant percentage of overall health care costs and contribute significantly to morbidity and mortality in the United States and around the world.
Berry fruits are widely consumed in our diet and have attracted much attention due to their poten... more Berry fruits are widely consumed in our diet and have attracted much attention due to their potential human health benefits. Berries contain a diverse range of phytochemicals with biological properties such as antioxidant, anticancer, anti-neurodegerative, and anti-inflammatory activities. In the current study, extracts of six popularly consumed berries--blackberry, black raspberry, blueberry, cranberry, red raspberry and strawberry--were evaluated for their phenolic constituents using high performance liquid chromatography with ultraviolet (HPLC-UV) and electrospray ionization mass spectrometry (LC-ESI-MS) detection. The major classes of berry phenolics were anthocyanins, flavonols, flavanols, ellagitannins, gallotannins, proanthocyanidins, and phenolic acids. The berry extracts were evaluated for their ability to inhibit the growth of human oral (KB, CAL-27), breast (MCF-7), colon (HT-29, HCT116), and prostate (LNCaP) tumor cell lines at concentrations ranging from 25 to 200 micro g/mL. With increasing concentration of berry extract, increasing inhibition of cell proliferation in all of the cell lines were observed, with different degrees of potency between cell lines. The berry extracts were also evaluated for their ability to stimulate apoptosis of the COX-2 expressing colon cancer cell line, HT-29. Black raspberry and strawberry extracts showed the most significant pro-apoptotic effects against this cell line. The data provided by the current study and from other laboratories warrants further investigation into the chemopreventive and chemotherapeutic effects of berries using in vivo models.
Most primary care physicians do not treat obesity, citing lack of time, resources, insurance reim... more Most primary care physicians do not treat obesity, citing lack of time, resources, insurance reimbursement, and knowledge of effective interventions as significant barriers. To address this need, a 10-minute intervention delivered by the primary care physician was coupled with individual dietary counseling sessions delivered by a registered dietitian via telephone with an automated calling system (House-Calls, Mobile, AL). Patients were seen for follow-up by their physician at weeks 4, 12, 24, 36 and 52. A total of 252 patients (202 women and 50 men) were referred by 18 primary care physicians to the program. The comorbid conditions reported for all patients at baseline included low back pain, 29% (n = 72); hypertension, 45% (n = 113); hypercholesterolemia, 41% (n = 104); type 2 diabetes, 10% (n = 26); and sleep apnea, 5% (n = 12). When offered a choice of meal plans based on foods or meal replacements, two-thirds of patients (n = 166) chose to use meal replacements (Ultra Slim-Fast; Slim-Fast Foods Co., West Palm Beach, FL) at least once daily. Baseline weights of subjects averaged 200 ± 46 lb for women (n = 202) and 237 ± 45 lb for men (n = 50). Patients completing 6 months in the program lost an average of 19.0 ± 4.0 lb for women (n = 94) and 15.5 ± 8.2 lb for men (n = 26). Physicians reported a high degree of satisfaction with the program, suggesting that a brief, effective physician-directed program with nutritionist support by telephone can be implemented in a busy primary care office.
Phytochemicals from fruits such as the pomegranate (Punica granatum L) may inhibit cancer cell pr... more Phytochemicals from fruits such as the pomegranate (Punica granatum L) may inhibit cancer cell proliferation and apoptosis through the modulation of cellular transcription factors and signaling proteins. In previous studies, pomegranate juice (PJ) and its ellagitannins inhibited proliferation and induced apoptosis in HT-29 colon cancer cells. The present study examined the effects of PJ on inflammatory cell signaling proteins in the HT-29 human colon cancer cell line. At a concentration of 50 mg/L PJ significantly suppressed TNFalpha-induced COX-2 protein expression by 79% (SE = 0.042), total pomegranate tannin extract (TPT) 55% (SE = 0.049), and punicalagin 48% (SE = 0.022). Additionally, PJ reduced phosphorylation of the p65 subunit and binding to the NFkappaB response element 6.4-fold. TPT suppressed NFkappaB binding 10-fold, punicalagin 3.6-fold, whereas ellagic acid (EA) (another pomegranate polyphenol) was ineffective. PJ also abolished TNFalpha-induced AKT activation, needed for NFkappaB activity. Therefore, the polyphenolic phytochemicals in the pomegranate can play an important role in the modulation of inflammatory cell signaling in colon cancer cells.
Phytoestrogens may function as partial agonists or antagonists of estrogen in many tissues includ... more Phytoestrogens may function as partial agonists or antagonists of estrogen in many tissues including bone. Five phytoestrogens, belonging to the isoflavones and the flavonoids groups, were assayed in the human MG-63 osteoblastic cell line for their ability to stimulate transcriptional activity of an estrogen-response element (ERE)-luciferase reporter gene via the estrogen receptor beta (ERbeta). Although MG-63 cells were shown to express endogenous estrogen receptors, estradiol (E2) did not affect transcriptional activity of an ERE reporter in these cells. However, E2 did activate the ERE-reporter significantly in MG-63 cells where ERbeta was overexpressed. The isoflavones, genistein and daidzein, caused a dose-dependent increase in the ERE-reporter activity in MG-63 cells overexpressing ERbeta. Among the flavonoids, kaempferol activated ERE-reporter activity, whereas puerarin inhibited ERE-reporter transcription in cells overexpressing ERbeta. Quercetin had no effect on ERE-reporter activity over a concentration range of 10(-10)-10(-6) mol/l. The ERE-reporter activity induced by daidzein, genistein, and kaempferol was blocked by both ICI 182780 and 4-hydroxytamoxifen and partly blocked by puerarin. Our results demonstrated that different phytoestrogens exhibited differential transcription activity of an ERE-reporter via ERbeta-mediated mechanisms in MG-63 cells.
Objective: Although weight management is an important component in the treatment of type 2 diabet... more Objective: Although weight management is an important component in the treatment of type 2 diabetes, there has been concern about the use of liquid meal replacements (MRs) in treating obese patients with type 2 diabetes because of the sugar content of the MRs. The goal of this study was to evaluate the safety and feasibility of using MRs for weight loss in obese patients with type 2 diabetes.Research Methods and Procedures: Seventy-five subjects with type 2 diabetes, treated only with oral agents, were recruited for this 12-week clinical study. Subjects were randomized into three groups using either a MR containing lactose, fructose, and sucrose, a MR in which fructose and sucrose were replaced with oligosaccharides (sugar-free Slim-Fast), or an exchange diet plan (EDP) using the proportion of macronutrients recommended by the American Diabetes Association.Results: Fifty-seven patients (41 MR and 16 EDP) finished the study. None developed serious adverse effects, including major hypoglycemic reactions. Weight losses in the MR 1 and MR 2 groups were comparable (6.4% and 6.7%, respectively) and greater than the weight loss in the EDP group (4.9%). Fasting glucose level was significantly reduced in the MR group compared with the EDP group (p = 0.012). There was a significant reduction in the MR group in total cholesterol and low-density lipoprotein cholesterol that was not seen in the EDP group.Discussion: We have shown that liquid MRs are a safe and effective weight loss tool for obese subjects with type 2 diabetes, and can result in improvements in body weight, glucose, insulin, hemoglobin A1c and lipid levels.
Strawberry (Fragaria x ananassa Duch.) fruits contain phenolic compounds that have antioxidant, a... more Strawberry (Fragaria x ananassa Duch.) fruits contain phenolic compounds that have antioxidant, anticancer, antiatherosclerotic and anti-neurodegenerative properties. Identification of food phenolics is necessary since their nature, size, solubility, degree and position of glycosylation and conjugation influence their absorption, distribution, metabolism and excretion in humans. Freeze-dried whole strawberry fruit powder and strawberry fruit extracts were analyzed by liquid chromatography electrospray ionization mass spectrometry (LC–ESI–MS) methods. Phenolics were identified as ellagic acid (EA), EA-glycosides, ellagitannins, gallotannins, anthocyanins, flavonols, flavanols and coumaroyl glycosides. The anthocyanidins were pelargonidin and cyanidin, found predominantly as their glucosides and rutinosides. The major flavonol aglycons were quercetin and kaempferol found as their glucuronides and glucosides. LC–ESI–MS/MS methods differentiated EA from quercetin conjugates since both aglycons have identical molecular weights (302g/mol). The identification of strawberry phenolics is necessary to generate standardized materials for in vitro and in vivo studies and for the authentication of strawberry-based food products.
Uploads
Papers by David Heber