Leukemia therapy by flavonoids: Future and involved mechanisms.

Flavonoids are a varied family of phytonutrients (plant chemicals) usually are detected in fruits and vegetables. In this big family, there exist more than 10,000 members that is separated into six chief subtypes: isoflavonols, flavonoenes, flavones, flavonols, anthocyanins, and chalcones. The natural compounds, such as fruits, have visible positive effects in regulating of survival involved signaling pathways that performance as the regulator of cell survival, growth, and proliferation. Researchers have established that commonly consumption up flavonoids decreases incidence and development risk of certain cancers, especially leukemia. Flavonoids have been able to induce apoptosis and stimulate cell cycle arrest in cancer cells via different pathways. Similarly, they have antiangiogenesis and antimetastasis capability, which were shown in wide ranges of cancer cells, particularly, leukemia. It seems that flavonoid because of their widespread approval, evident safety and low rate of side effects, have hopeful anticarcinogenic potential for leukemia therapy. Based on the last decade reports, the most important acting mechanisms of these natural compounds in leukemia cells are stimulating of apoptosis pathways by upregulation of caspase 3, 8, 9 and poly ADP-ribose polymerase (PARP) and proapoptotic proteins, particularly Bax activation. As well, they can induce cell cycle arrest in target cells not only via increasing of activated levels of p21 and p53 but also by inhibition of cyclins and cyclin-dependent kinases. Furthermore, attenuation of neclear factor-κB and signal transducer and activator of transcription 3 activation, suppression of signaling pathway and downregulation of intracellular antiapoptotic proteins are other significant antileukemic function mechanism of flavonoids. Overall, it appears that flavonoids are promising and effective compounds in the field of leukemia therapy. In this review, we tried to accumulate and revise most promising flavonoids and finally declared their major working mechanisms in leukemia cells.

Questioning the role of a neutropenic diet following hematopoetic stem cell transplantation.

The use of a neutropenic diet (ND) after hematopoietic stem cell transplantation (HSCT) was instituted more than 30 years ago as a means of preventing infection from organisms colonizing the gastrointestinal tract. Evidence supporting this practice is lacking, however, and the actual efficacy of the ND remains unknown. Institutional policy at Northwestern Memorial Hospital discontinued the use of ND in 2006. We conducted a retrospective study of 726 consecutive HSCT recipients, 363 who received an ND and 363 who received a general hospital diet, to determine the incidence of microbiologically confirmed infections during and after transplantation. Our findings indicate a higher rate of infections in the HSCT recipients who received an ND.

Retrospective robustness of the continual reassessment method.

We study model sensitivity of the continual reassessment method (CRM). The context is that of dose-finding designs where certain design parameters are fixed by the investigator. Although our focus is on the CRM (O'Quigley et al., 1990), the essential ideas can be applied to any sequential dose-finding method. It is expected that different choices of a model family and particular parameterizations will have an impact on performance. Assuming that the constraints outlined in Shen and O'Quigley (1996) are respected, large sample performance is unaffected. However small sample performance will be affected by these choices, which are to some degree arbitrary. This work focuses on the retrospective robustness of the CRM in practice. The question is not of a general theoretical nature where, in the background, we would want to consider large numbers of true potential situations. Instead, the question is raised in the specific context of any actual completed study and is the following: Would we have come to the same conclusion concerning the MTD had we worked with a design specified differently? The sequential nature of the CRM means that this question cannot be answered in any definitive way. We can, though, by appealing to the retrospective CRM (O'Quigley, 2005), provide consistent estimates of the relationships between the MTD and the chosen model. If these estimates suggest that changes in different family model parameters will be accompanied by changes in final recommendation, then we would not be confident in the reliability of the estimated MTD and more work would be needed. Also, of course, at the planning stage, prospective robustness could be studied by simulating trials using particular models and parameterizations.

Effects of vinegar-egg on growth inhibition, differentiation human leukemic U937 cells and its immunomodulatory activity.

Vinegar and eggs have rich nutrients. In this study, the mixed form of both derived products, vinegar-egg solution and its products (vinegar-egg concentrate and vinegar-egg condensate) were chosen for an assessment of their biological activity. To further our understanding regarding the anticancer and immunomodulatory effects of vinegar-egg, we investigated its effects on the proliferation and differentiation of U937 cells. Vinegar-egg was treated using spray drying, freeze drying and vacuum concentration and used to stimulate human mononuclear cells. The conditioned media obtained from these cultures by filtration were used to treat U937 cells. Three conditioned media inhibited U937 cell growth by 22.1-67.25% more effectively than PHA-treated control (22.53%). CD11b and CD14 expression on the treated U937 cells were 29.1-45.4% and 31.6-47.2%, respectively. High levels of cytokines IL-1ß, IFN-γ and TNF-α were detected in the three conditioned media. Vinegar-egg stimulates human mononuclear cells to secrete cytokines, which inhibit the growth of U937 cells and induce their differentiation.

Laminarin Promotes Immune Responses and Normalizes Glutamic Oxaloacetic Transaminase and Glutamic Pyruvic Transaminase Levels in Leukemic Mice In Vivo.

BACKGROUND/AIM: Laminarin, mainly found in the fronds of Laminaria, has antimicrobial characteristics and induces immune responses. However, there are no available information to show the laminarin effect on glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels in mice with leukemia in vivo. MATERIALS AND METHODS: Fifty normal BALB/c mice were separated randomly into five groups. Group I mice received normal diet as control. Leukemia was generated in groups II-V using WEHI-3 cells: Group II mice received normal diet as positive control; group III, IV and V mice received laminarin at 1, 2.5 and 5 mg/ml with ddH2O, respectively, by oral gavage every 2 days for 14 days (total of seven times). All mice were weighed during the treatment. After treatment, mice were sacrificed, blood was collected for determination of cell markers, liver and spleen samples were weighed, and spleens were used for phagocytosis and natural killer (NK) cell activity and cell proliferation using flow cytometric assay. RESULTS: Laminarin did not affect animal appearances, but increased the body weight at all doses. It reduced the weight of liver at 2.5 and 5 mg/ml and of spleen at 5 mg/ml. Laminarin increased CD3 (2.5 mg/ml) and CD19 (1 and 5 mg/ml) cell populations but reduced CD11b (5 mg/ml) cell populations, however, these did not affect Mac-3 marker level. Laminarin at 1 mg/ml increased phagocytosis by macrophages from peripheral blood mononuclear cell, but did not affect those from the peritoneal cavity. Laminarin increased NK cell cytotoxic activity at all doses and at a target ratio of 25:1 and 50:1. Laminarin did not affect B-cell proliferation, but at 5 mg/ml significantly reduced T-cell proliferation. Laminarin restored glutamate oxaloacetate transaminase (2.5 and 5 mg/ml) and glutamate pyruvate transaminase (2.5 mg/ml) levels. Based on these results, we suggest that laminarin can promote immune responses and protect against liver injury.

Kefir: a powerful probiotics with anticancer properties.

Probiotics and fermented milk products have attracted the attention of scientists from various fields, such as health care, industry and pharmacy. In recent years, reports have shown that dietary probiotics such as kefir have a great potential for cancer prevention and treatment. Kefir is fermented milk with Caucasian and Tibet origin, made from the incubation of kefir grains with raw milk or water. Kefir grains are a mixture of yeast and bacteria, living in a symbiotic association. Antibacterial, antifungal, anti-allergic and anti-inflammatory effects are some of the health beneficial properties of kefir grains. Furthermore, it is suggested that some of the bioactive compounds of kefir such as polysaccharides and peptides have great potential for inhibition of proliferation and induction of apoptosis in tumor cells. Many studies revealed that kefir acts on different cancers such as colorectal cancer, malignant T lymphocytes, breast cancer and lung carcinoma. In this review, we have focused on anticancer properties of kefir.

Temas para Construção de Material Educativo sobre Alimentação da Criança com Leucemia / Themes for the Construction of Educational Material about Feeding Children with Leukemia / Temas para la Construcción de Material Educativo sobre Alimentación de Niños con Leucemia

Introdução: A alimentação é um tema que gera muitas dúvidas nos familiares de crianças com leucemia, e os materiais educativos são fundamentais para preparar e orientar esses cuidadores para o cuidado domiciliar. Objetivo: Identificar os temas sobre a alimentação da criança com leucemia sob a ótica de enfermeiros e familiares cuidadores para construção de material educativo. Método: Pesquisa qualitativa participativa realizada em 2018 por meio de círculos de discussão, em um hospital oncológico no Rio de Janeiro-RJ, com seis familiares e seis enfermeiros, após aprovação dos Comitês de Ética em Pesquisa. Os dados foram analisados pelo método da análise de conteúdo na modalidade temático-categorial. Resultados: As falas dos familiares e enfermeiros subsidiaram o conteúdo para construção de materiais educativos, como cartilha, apontando a necessidade de orientações sobre alimentação oferecida à criança, destacando os seguintes temas: imunidade normal; neutropenia; náuseas e vômitos; mucosite; disgeusia; constipação; diarreia; higiene e forma de preparo dos alimentos. Conclusão: A construção de material educativo para familiares de crianças com leucemia poderá contribuir para sanar as dúvidas dos familiares, uma vez que permitirá aos enfermeiros orientá-los durante a internação de sua criança, servindo posteriormente como um guia para o desenvolvimento dos cuidados de sua criança no domicílio

Introduction: Food is a theme that raises many doubts in family members of children with leukemia and educational materials are essential to prepare and guide these caregivers for home care. Objective: To identify the topics on feeding children with leukemia from the perspective of nurses and family caregivers for the construction of educational material. Method: Qualitative participatory research conducted in 2018 through discussion circles, in an oncology hospital in Rio de Janeiro-RJ, with 6 family members and 6 nurses, after approval by the Institutional Review Board. The data were analyzed using the content analysis method in the thematic-categorical modality. Results: The narratives of family members and nurses were utilized to elaborate the content for the construction of educational materials such as primes, pointing out the need for guidance on food offered to the child, focusing on the following themes: normal immunity; neutropenia; nausea and vomiting; mucositis; dysgeusia; constipation; diarrhea; hygiene and food preparation. Conclusion: The construction of educational material for family members of children with leukemia may help to respond to their doubts, since it will enable nurses to guide them during the hospitalization, and later working as a guide for the development of their child's home care

Introducción: La alimentación es un tema que genera muchas dudas en los familiares de los niños con leucemia y los materiales educativos son fundamentales para preparar y orientar a estos cuidadores para el cuidado domiciliario. Objetivo: Identificar los temas de alimentación infantil con leucemia desde la perspectiva de enfermeras y cuidadores familiares para la construcción de material educativo. Método: Investigación cualitativa participativa realizada en 2018 a través de círculos de discusión, en un hospital oncológico de Rio de Janeiro-RJ, con seis familiares y seis enfermeros, previa aprobación de los Comités de Ética en Investigación. Los datos fueron analizados mediante el método de análisis de contenido en la modalidad temática-categórica. Resultados: Los discursos de familiares y enfermeras fueron utilizados para elaborar contenido para la construcción de materiales educativos como el cuadernillo, señalando la necesidad de orientación sobre la alimentación ofrecida al niño, centrándose en los siguientes temas: inmunidad normal; neutropenia náuseas y vómitos; mucositis; disgeusia; constipación; diarrea; higiene y forma de preparación de los alimentos. Conclusión: La construcción de material educativo para familiares de niños con leucemia puede ayudar a resolver las dudas, ya que permitirá al enfermero orientarlos durante la hospitalización de su hijo, sirviendo posteriormente como guía para el desarrollo del cuidado en el domicilio

[Clinico-metabolic effects of biologically active phospholipid and pectin additives in patients with acute leukemia]. / Kliniko-metabolicheskie éffekty biologicheski aktivnykh dobavok fosfolipidnoi i pektinovoi prirody u bol'nykh ostrym leikozom.

Antioxidant and membranoprotective effect of biological active supplements of phospholipid and pectin nature in patients with acute leukosis during the clinical and laboratory remission period is indicated.

Enteral nutrition: a first option for nutritional support of children following allo-SCT?

Parenteral nutrition (PN) is the treatment of choice for nutritional support of patients undergoing allo-SCT following myeloablative conditioning (MAC). Here we prospectively assessed the outcomes of early enteral nutrition (EN) in a paediatric cohort. From 2003 to 2010, all 65 consecutive children undergoing MAC allo-SCT at our referral centre began EN the day after transplantation. Post-transplant and nutritional outcomes of patients receiving only EN (EN group, n=50) were compared with those of patients requiring additional PN (EN-PN group, n=15). In the EN group time to platelet recovery (P=0.01) and length of hospitalisation (P<0.001) were shorter, while in the EN-PN group the proportion of unrelated donors (P=0.02) and the frequency of severe acute GVHD (aGVHD; P=0.004) were higher. All patients were alive at day 100. PN was started 14 days after transplant because of poor digestive tolerance to EN or severe gut aGVHD. The body mass index Z-score in the EN-PN group decreased from transplant to discharge (P=0.02). In only 23% of cases was PN required for severely ill patients. Our results suggest that EN might be considered to be an option for nutritional support in children undergoing MAC allo-SCT, while PN should be used only as a rescue option, possibly in combination with EN.

In vivo and in vitro antitumor effects of nutrient mixture in murine leukemia cell line P-388.

AIM: Leukemia is characterized by uncontrolled marrow cell proliferation and metastatic foci. We investigated the antitumor potential of a nutrient mixture on malignant leukemia P-388 cells. METHODS: The nutrient mixture containing lysine, proline, ascorbic acid, green tea extract and other nutrients is formulated to target key pathways in cancer progression. The cells were treated with the mixture, and tested at doses 0, 10, 50, 100, 500 and 1000 µg/ml in triplicates. The effects were evaluated by cell proliferation, Matrigel invasion, cell morphology and apoptosis. The in vivo effect was measured in male nude mice (n = 12) inoculated with P-388 cells. After randomly dividing in two groups, each group was fed regular and the nutrient mixture supplemented diet and the mice were sacrificed after four weeks. RESULTS: The nutrient mixture decreased P-388 cell proliferation at 500 and 1000 µg/ml. Only 10% cells were viable at 1000 µg/ml. Matrigel invasion was significantly inhibited in a dose dependent manner with virtually total inhibition at 1000 µg/ml. Cell morphological features notably changed with dose increase to 1000 µg/ml. Analysis of apoptotic cells on live green caspase kit exhibited gradual increase with the increasing dose of the nutrient mixture, and at 1000 µg/ ml 92% of P-388 cells were in late apoptosis. Tumors in the group of mice supplemented with the nutrient mixture had 50% lower weight compared to the tumors in control group (p = 0.0105). Histopathologically, both the groups of tumors were similar, yet size of tumors in the group treated with the nutrient mixture was considerably smaller. CONCLUSION: These results indicate that the nutrient mixture exhibited significant action against multiple targets in P-388 leukemia and may have potential in human leukemia.

The cure of advanced cancer by diet therapy: a summary of 30 years of clinical experimentation.

Thirty years of clinical experimentation has led to a successful therapy for advanced cancer. This therapy is based on the concepts (1) that cancer patients have low immuno-reactivity and generalized tissue damage, especially of the liver, and (2) that when the cancer is destroyed, toxic degradation products appear in the bloodstream which lead to coma and death from liver failure. The therapy consists of high potassium, low sodium diet, with no fats or oils, and minimal animal proteins. Juices of raw fruits and vegetables and of raw liver provide active oxidizing enzymes which facilitate rehabilitation of the liver. Iodine and niacin supplementation is used. Caffeine enemas cause dilation of bile ducts, which facilitates excretion of toxic cancer breakdown products by the liver and dialysis of toxic products from blood across the colonic wall. The therapy must be used as an integrated whole. Parts of the therapy used in isolation will not be successful. This therapy has cured many cases of advanced cancer.

Effect of total parenteral nutrition on marrow recovery during induction therapy for acute nonlymphocytic leukemia in childhood.

Ten well-nourished children with acute nonlymphocytic leukemia (ANLL) were randomly assigned to groups that received (a) total parenteral nutrition (TPN) throughout the period of induction therapy or (b) standard nutritional support. Body mass and skin hypersensitivity reactions were better maintained in experimental patients. Patients on TPN had higher total white blood counts, absolute granulocyte counts, and platelet counts than did control patients during the course. No difference was apparent in the frequency of febrile episodes, or other aspects of the patients' courses. This preliminary report suggests that intensive nutritional support may accelerate the recovery of normal marrow function during induction therapy for ANLL.

Change in energy and protein status during chemotherapy in patients with acute leukemia.

The energy and protein status of 12 adult patients with acute leukemia (AL) was investigated during induction chemotherapy. Parenteral nutrition (PN) (nonprotein [NP], 31.4 kcal/kg/d; nitrogen [N], 0.177 g/kg/d) was started on day 6 after the beginning of chemotherapy and continued through all of the cytopenic phase. A clinical and metabolic evaluation, including measurement of resting energy expenditure (REE) by indirect calorimetry, was performed on each patient within the 2 days before beginning chemotherapy (D0), on the third day of chemotherapy (D3), and then weekly from day 7 until the end of the cytopenic phase. Measured REE at day 0 (29.5 +/- 1.4 kcal/kg/d) was significantly higher (+34 +/- 6%) than theoretical REE. Chemotherapy induced a significant decrease in REE at day 3 (26.2 +/- 1.7 kcal/kg/d; P less than 0.05), but during the cytopenic phase REE was not different significantly from its initial values (D0). A positive energy balance was observed during the whole study after the beginning of PN. In contrast, mean nitrogen balance remained negative always, due to a sharp increase in urinary nitrogen loss during the cytopenic phase. The fact that nutritional support falls short of its goal may explain why no improvement in tumor response to therapy has been described in most studies.