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The effect of fermented soy (FSWW08) on blood hematology and cachexia in cancer patients

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Abstract

Abstract In cancer patients, appetite and immune status are significantly weakened. Two experimental fermented formulations without (group A, named as FSWW08) and with (group B, FSWW08) an extract from yam root were investigated against a placebo formulation with casein (group C) in a clinical study conducted in six cancer hospitals where cancer patients underwent radio or chemotherapy (patients undergoing radiation therapy n=78, patients undergoing chemotherapy n=184, total 262). IgG and IgA were increased by formulation A in patients despite receiving radio- or chemotherapy. Group A experienced statistically significant increases in lymphocyte transformation rates, whereas group B and group C did not. Formulations A and B either inhibited or lessened statistically significant decreases in white blood counts, whereas the placebo group experienced substantial decreases. Hemoglobin and platelet decreases were inhibited in group A, although not statistically significantly. Patients in group A received no blood transfusions, whereas many patients from the placebo group received blood transfusions. Appetite loss was reduced in group A from 57.9% to 13.3% and in group B from 70% to 35.8%. In the placebo group, an increase in appetite loss was detected under chemo and radiation therapy from 41.8% to 70.9%.

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... This paper therefore systematically investigates the effect of fermented soy bean formulation on cancer cells in vitro, as was shown by others also, in vivo in CTC extracted from blood from cancer patients, which has not been shown before. We detected and reported earlier that the effectiveness of chemotherapy was increased by fermented soy formulation, side effects were reduced, and survival increased [39,40]. This study investigates in vitro whether a combination of the classic cytotoxic compound doxorubicin may be combined with fermented soy bean and counterbalance some of the side effects of classical chemotherapy on the genetic level. ...
... The study protocol was reviewed by a local institutional review board (IRB) to protect the rights of patients, safety and well-being of humans involved in a clinical trial by reviewing all aspects of the trial and approving its startup and was published previously [24,39,40]. All patients had to sign an Informed Consent Form after the physician explained the study and he read the informed consent form where the study goal was outlined in a written form, in which the study was outlined and participation was voluntarily and it was explained individually to all patients that they could leave the study at any time even without explanation. ...
... All in vitro procedures determining the gene expression determination have been described before [24,39,40,44], however a more thorough investigation and discussion about in vitro and in vivo comparison and DNA repair is missing. Investigations of the human breast cancer cell line BT-474 were conducted, which were purchased from the German National Resource ...
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The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anticancer drugs targeting cancer stem cells. Naturally occurring dietary compounds have received increasing attention in cancer chemoprevention. The anticancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine and vitamin D(3), are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor-initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival.
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To investigate the cytotoxic activity against lung cancer cells of Dioscorea birmanica Prain & Burkill extract and its compounds. Cytotoxic activity was tested against two types of lung cancer cell line (A549 and CORL-23), one type of normal lung cell (MRC-5) by sulforhodamine B assay. Bioassay guide fractionation was used for isolating cytotoxic compounds. The structure elucidation of active ingredients was proven by spectrophotometry technique. The results found that the ethanolic extract of Dioscorea birmanica Prain & Burkill (DBE) showed high cytotoxic activity against lung cancer cells; A 549 and COR-L23 (IC50 = 7.45 +/- 0.31, 8.71 +/- 0.29 microg/ml, respectively) but no cytotoxic activity against normal cancer cells MRC-5 (IC50 = 94.76 +/- 1.25 micro/ml). Six fractions from DBE were isolated by vaccuum liquid chromatography with ordering polarity of solvent and were coded as DB1-DB6, respectively. The fraction DB5 showed high cytotoxic against A 549 and COR-L23 (IC50 = 6.14 +/- 0.08 and 16.44 +/- 1.23 microg/ml, respectively) but less toxic to normal cell. Diosgenin-3-O-alpha-L-rhamnosyl (1-->2)-beta-D-glucopyranoside or Prosapogenin A of dioscin (DBS1) was isolated from DB5 fraction and had highest cytotoxic activity against those two types of lung cancer cells (IC50 = 1.81 +/- 0.03, 1.84 +/- 0.05 microg/ml), respectively) but less cytotoxic against normal lung cells MRC-5 (IC50 = 37.09 +/- 0.67 microg/ml). The steroid saponin from Dioscorea birmanica showed cytotoxic activity against human lung cancer cells but less toxic against normal lung cells.
Article
To estimate the effect of independent practice association (IPA) model HMOs and the Kaiser Foundation Health Plan's group model on inpatient utilization of Medicare beneficiaries in the last 2 years of life, compared with traditional fee-for-service (FFS) coverage. Data from the Centers for Medicare & Medicaid Services were linked to inpatient discharge data from the California Office of Statewide Health Planning and Development for 1991-2001. A sample of aged Medicare beneficiaries who died between January 1998 and June 2001 and were continuously enrolled during the 2 years before death in (1) FFS (n = 234,498), (2) an IPA (n = 109,577), or (3) Kaiser (n = 29,434) were selected. The probability of at least 1 hospitalization, number of inpatient days given at least 1 hospitalization, and total inpatient days per year in the last 2 years of life were estimated for each subgroup. A 2-part regression model, which adjusted for age, sex, Medicaid status, race, ethnicity, and chronic condition associated with the last hospitalization, was applied to determine the HMO-FFS difference in inpatient utilization during the last 2 years of life. During their last 2 years of life, decedents in IPAs and Kaiser used approximately 34% and 51% fewer inpatient days, respectively, than decedents in FFS. Medicare beneficiaries who died while enrolled in an HMO, particularly Kaiser, had many fewer hospital days during the 2 years before death than beneficiaries who died with FFS coverage.
Article
Cachexia represents the clinical consequence of a chronic, systemic inflammatory response, and its manifestations differ considerably from those of starvation. Although cachexia is classically associated with chronic infections and malignant conditions, some of its elements have been identified in a wide variety of chronic diseases and in aging persons. Cachexia has repeatedly been associated with adverse clinical outcomes. The changes seen in cachexia are multidimensional and highly coordinated. Most obvious is a redistribution of the body's protein content, with preferential depletion of skeletal muscle and an increase in the synthesis of proteins involved in the response to tissue injury-the so-called acute-phase response. The physiologic, metabolic, and behavioral changes of cachexia are tightly regulated by cytokines, which signal the synthesis of acute-phase proteins as well as changes in intermediary metabolism that provide substrate and energy. The metabolic adaptations, notably the increase in the rate of protein degradation, limit the ability of hypercaloric feeding to reverse the depletion of lean mass. Recent studies have demonstrated the ability of anabolic and anticatabolic agents to mitigate the loss of skeletal muscle and to improve clinical outcomes in selected circumstances. Preclinical initiatives target the cytokine regulation of protein metabolism. It should be stressed that metabolic manipulation in cachexia could have positive or negative clinical effects, which must be distinguished through appropriate clinical trials.
Article
Beginning with its discovery in 1986 and continuing through the present, the transcription factor NF-κB has attracted widespread interest based on its unusual regulation, the variety of stimuli that activate it, the diverse genes and biological responses that it controls, the striking evolutionary conservation of structure and function among family members, and its apparent involvement in a variety of human diseases (Table (Table1).1). Importantly, and consistent with the last point, NF-κB has been shown to be the target of several anti-inflammatory and anticancer drugs.
Article
In most cells, the NF-kappaB transcription factor is sequestered in the cytoplasm by interaction with inhibitory proteins, the IkappaBs. Here, we show that combined IkappaBalpha/IkappaBepsilon deficiency in mice leads to neonatal death, elevated kappaB binding activity, overexpression of NF-kappaB target genes, and disruption of lymphocyte production. In IkappaBalpha/IkappaBepsilon-deficient fetuses, B220+IgM+ B cells and single-positive T cells die by apoptosis. In adults, IkappaBalpha-/-IkappaBepsilon-/- reconstituted chimeras exhibit a nearly complete absence of T and B cells that is not rescued by cotransfer with wild-type bone marrow. These findings demonstrate that IkappaBs tightly control NF-kappaB activity in vivo and that increased NF-kappaB activity intrinsically impairs lymphocyte survival. Because reduction or rise of NF-kappaB activity leads to similar dysfunction, they also reveal that only a narrow window of NF-kappaB activity is tolerated by lymphocytes.
Article
Since it is known that androstenediol (ADIOL) has potent immunoregulatory effects, changes in ADIOL levels during and after pregnancy might affect the maternal immune system. We examined serum concentrations of ADIOL and androstenediol 3-sulfate (ADIOLS) together with IFN-gamma and IL-4 production levels during pregnancy and after delivery up to 10-11 months postpartum. The subjects were 73 normal pregnant, 76 normal postpartum, and 28 normal non-pregnant women. ADIOL and ADIOLS were measured using EIA and GC/MS, respectively. The cytokine levels in the supernatant of whole-blood cultures stimulated with phorbol 12-myristate 13-acetate and ionomycin were measured using ELISA. ADIOL levels significantly decreased compared to non-pregnant levels in the first trimester (P < 0.05) and were reversed in the third trimester (P < 0.05). After pregnancy, ADIOL levels gradually declined, and a significant decrease was observed at 10-11 months postpartum (P < 0.05). ADIOLS levels were significantly lower in the third trimester (P < 0.05) and significantly higher at the first month postpartum (P < 0.001) compared to non-pregnant women. IFN-gamma and IL-4 levels decreased during pregnancy and subsequently increased postpartum. On the other hand, we found significant negative correlations between ADIOL concentrations and production levels of IFN-gamma (P < 0.05) or IL-4 (P < 0.05). These findings suggest that ADIOL may be involved in modifying the maternal immune response during and after pregnancy.
Article
Radiation protection from death and stimulating hematopoietic recovery by oral administrations of genistein, 160 mg/kg b.w., once daily for seven consecutive days before whole-body gamma-rays irradiation, were confirmed by tests with adult male BALB/c mice. Moreover, the protective action of genistein was compared to that of diethylstilbestrol (DES). Based on the studies of survival, behavior of hematograms, endogenous hematopoietic spleen colony formation (endoCFUs), and numbers of nucleated cell, granulocyte-macrophage colony forming units (CFU-GM) in bone marrow following irradiation, it was demonstrated that genistein was an effective radioprotector. The survival of irradiated mice protected by genistein was significantly increased and statistically higher than that of mice pre-treated with DES. Stimulated recovery of leukocytes, erythrocytes, lymphocytes and thrombocytes were observed in mice pre-treated with genistein or DES, however, the effects of genistein on promoting recovery of bone marrow nucleated cells, leukocytes and lymphocytes were significantly higher than those of DES. Enhanced endoCFUs, numbers of bone marrow nucleated cells and CFU-GM were also found in mice pre-treated with genistein as well as DES. Meanwhile, endoCFU numbers in mice pre-treated with genistein was 3.47-fold higher than that in the irradiated control group, although no significant difference was found between genistein administration and DES administration. It could be deduced that the radioprotective action against death is induced by a possible process of enhanced regeneration of the hematopoietic stem cells due to not only strengthened radioresistance and increased numbers of remained hematopoietic cells, but also enhanced post-irradiation repair or promoted proliferation of the hematopoietic stem cells. These effects of genistein may have some therapeutic implications for radiation-induced injuries.
Article
Although androstenediol (adiol or 5-androstene-3beta,17beta-diol), a metabolite of dehydroepiandrosterone (DHEA), has protective effects following trauma-hemorrhage (T-H), it remains unknown whether administration of adiol has any salutary effects on the inflammatory response and outcome following a combined insult of T-H and sepsis. Male rats underwent T-H shock [mean arterial pressure (MAP) 40 mmHg for 90 min] followed by resuscitation. Adiol (1 mg/kg body wt) or vehicle was administered at the end of resuscitation. Sepsis was induced by cecal ligation and puncture (CLP) at 20 h after T-H or sham operation. Five hours after CLP, plasma and tissue samples were analyzed for cytokines (IL-6 and IL-10), MPO, neutrophil chemotactic factor (CINC-3), and liver injury (alanine aminotransferase and lactate dehydrogenase). In another group of rats, the gangrenous cecum was removed at 10 h after CLP, the cavity was irrigated with warm saline and closed in layers, and mortality was recorded over 10 days. T-H followed by CLP produced a significant elevation in plasma IL-6 and IL-10 levels, enhanced neutrophil cell activation, and resulted in liver injury. Adiol administration prevented the increase in cytokine production, neutrophil cell activation, and attenuated liver injury. Moreover, rats subjected to the combined insult, receiving vehicle or adiol, had a 50% and 6% mortality, respectively. Since adiol administration suppresses proinflammatory cytokines, reduces liver damage, and decreases mortality after the combined insult of T-H and sepsis, this agent appears to be a novel adjunct to fluid resuscitation for decreasing T-H-induced septic complications and mortality.
Article
5-Androstenediol (5-AED) stimulates hematopoiesis and enhances survival in animals exposed to ionizing radiation (IR), suggesting that this steroid may act on hematopoietic progenitor cells. We used gamma-irradiated primary human CD34(+) hematopoietic progenitor cells to show that 5-AED protects hematopoietic cells from IR damage, as shown by enhanced cell survival, clonogenicity, proliferation, and differentiation. Unlike in tumor cells, IR did not induce nuclear factor-kappaB (NFkappaB) activation in primary progenitors. However, IR stimulated IkappaB(beta) release from NFkappaB/IkappaB complexes and caused NFkappaB1 (p50) degradation. 5-AED stabilized NFkappaB1 in irradiated cells and induced NFkappaB gene expression and NFkappaB activation (DNA binding). 5-AED stimulated interleukin-6 and granulocyte colony-stimulating factor (G-CSF) secretion. The survival-enhancing effects of 5-AED on clonogenic cells were abrogated by small interfering RNA inhibition of NFkappaB gene expression and by neutralization of G-CSF with antibody. The effects of 5-AED on survival and G-CSF secretion were blocked by the NFkappaB inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132). 5-AED had no effect on accumulation of the proapoptotic factor p53 after IR, as determined by Western blot. The results indicate that NFkappaB1 degradation after IR may be responsible for the radiation sensitivity of CD34+ cells compared with tumor cells. 5-AED exerts survival-enhancing effects on irradiated human hematopoietic progenitor cells via induction, stabilization, and activation of NFkappaB, which results in increased secretion of hematopoietic growth factor G-CSF.
Article
Nuclear factor-kappaB pathway plays important roles in the control of cell proliferation, differentiation, apoptosis, inflammation, stress response, cell signaling transduction, and other physiological processes. Because the disorder of these physiological processes has been linked with the onset of cancers, NF-kappaB has been described as a major culprit in cancer. Experimental in vitro and in vivo studies have shown that down-regulation of NF-kappaB activity by natural and synthetic NF-kappaB inhibitors suppresses the development of carcinogen-induced tumors, inhibits the growth of cancer cells, and induces apoptosis with alternation of gene expression which is critical for the control of carcinogenesis and cancer cell survival. Moreover, recent studies indicate that the effects of conventional cancer therapeutics could be enhanced by natural and synthetic NF-kappaB inhibitors, suggesting that down-regulation of NF-kappaB could sensitize cancer cells to conventional therapeutics. Therefore, targeting NF-kappaB is a novel preventive and therapeutic strategy against human cancers. In this brief review article, we will summarize the state of our knowledge for the role of NF-kappaB in relation to cancer prevention and therapy.
Article
Objective: In April 2005 a phase III randomized study was started to establish which was the most effective and safest treatment of cancer-related anorexia/cachexia syndrome and oxidative stress in improving identified primary endpoints: increase of lean body mass, decrease of resting energy expenditure (REE), increase of total daily physical activity, decrease of interleukin-6 and tumor necrosis factor-alpha, and improvement of fatigue assessed by the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Methods: All patients were given as basic treatment polyphenols plus antioxidant agents alpha-lipoic acid, carbocysteine, and vitamins A, C, and E, all orally. Patients were then randomized to one of the following five arms: 1) medroxyprogesterone acetate/megestrol acetate; 2) pharmacologic nutritional support containing eicosapentaenoic acid; 3) L-carnitine; 4) thalidomide; or 5) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus L-carnitine plus thalidomide. Treatment duration was 4 mo. The sample comprised 475 patients. Results: By January 2007, 125 patients, well balanced for all clinical characteristics, were included. No severe side effects were observed. As for efficacy, an interim analysis on 125 patients showed an improvement of at least one primary endpoint in arms 3, 4, and 5, whereas arm 2 showed a significant worsening of lean body mass, REE, and MFSI-SF. Analysis of variance comparing the change of primary endpoints between arms showed a significant improvement of REE in favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor of arms 1, 3, and 5 versus arm 2. A significant inferiority of arm 2 versus arms 3, 4, and 5 for the primary endpoints lean body mass, REE, and MFSI-SF was observed on the basis of t test for changes. Conclusion: The interim results obtained thus far seem to suggest that the most effective treatment for cancer-related anorexia/cachexia syndrome and oxidative stress should be a combination regimen. The study is still in progress and the final results should confirm these data.
Article
A benign human plexiform neurofibroma cell. Note the extensive tubulin networks (red), which become disrupted after addition of 2ME2, an estrogen metabolite implicated in tumor toxicity. The green staining represents S100 staining, indicating the Schwann Cell origin of the tumor cells. Blue is DAPI nuclear staining. See Roth et al., Developmental Dynamics 237:513-524, 2008. (c) 2008 Wiley-Liss, Inc.
Article
Malignant effusions offer a unique opportunity for the study of interactions between the human immune system and cancer. We have recently demonstrated that malignant effusions are characterized by an accumulation of T cells expressing chemokine receptors such as CCR4, which is commonly found on Th2 cells. In contrast, effector T cells expressing chemokine receptors typical for Th1 cells, such as CCR5, showed a diminished homing into malignant effusions. We analyzed concentrations of 12 different cytokines and 9 chemokines within malignant and nonmalignant effusions and investigated cytokine expression by effusion-infiltrating leukocytes. We observed that concentrations of the immunoregulatory cytokine TGF-beta(1) and of angiogenic factors VEGF and IL-8 were markedly increased within effusions caused by malignancies. However, we did not observe signs of a typical Th1 or Th2 milieu. Analyzing concentrations of 9 different chemokines, we found elevated concentrations of the chemokines MDC, eotaxin, I-TAC, and MCP-1 in malignant effusions. Interestingly, tumor-infiltrating leukocytes themselves seemed to contribute strongly to the creation of a distinct cytokine/chemokine pattern within cancer-related effusions. Additional analyses suggested that this cytokine/chemokine milieu might support an enrichment of immunosuppressive leukocytes. The local cytokine and chemokine milieu within malignant effusions seems to promote angiogenesis and to block an efficient immune-mediated antitumor response. An elimination of such tumor-promoting influences will be necessary in order to transform local immunotolerance into clinically relevant immune recognition of tumors causing malignant effusions.
Article
Transforming growth factor beta-activated kinase 1 (TAK1), a member of the MAPKKK family, is a key mediator of proinflammatory and stress signals. Activation of TAK1 by proinflammatory cytokines and T and B cell receptors induces the nuclear localization of nuclear factor kappaB (NF-kappaB) and the activation of c-Jun N-terminal kinase (JNK)/AP1 and P38, which play important roles in mediating inflammation, immune responses, T and B cell activation, and epithelial cell survival. Here, we report that TAK1 is critical for the survival of both hematopoietic cells and hepatocytes. Deletion of TAK1 results in bone marrow (BM) and liver failure in mice due to the massive apoptotic death of hematopoietic cells and hepatocytes. Hematopoietic stem cells and progenitors were among those hematopoietic cells affected by TAK1 deletion-induced cell death. This apoptotic cell death is autonomous, as demonstrated by reciprocal BM transplantation. Deletion of TAK1 resulted in the inactivation of both JNK and NF-kappaB signaling, as well as the down-regulation of expression of prosurvival genes.
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Physiologischer Einfluss adrenaler Androgene und Glucocorticoide auf den Unterarmknochen im Wachstumsalter bei gesunden Kindern Dissertation Available athttp www diss fu berlin de
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