Gamma processing of Arabic bread for immune system-compromised cancer patients.

Arabic bread prepared from local Saudi flour contained a total of up to 10(4) organisms per g. Most of these were bacterial spores that survived the baking process (1.3 X 10(2) to 3.5 X 10(3] and a small number of yeasts and molds (10 to 40 cells per g). The organisms in Arabic bread appear to be harmless to healthy individuals. However, for immune system-compromised cancer patients and bone marrow transplant recipients, it is prudent to irradiate the bread to reduce microbial contamination. The decimal reduction doses (10% survival) for the most radiation-resistant organisms (spore formers) in bread were 0.11 to 0.15 Mrad. Accordingly, 0.6 Mrad was sufficient to reduce the number of spores in Arabic bread by a factor of 10,000, i.e., to less than 1/g. This treatment constitutes radiation pasteurization (radicidation), and to this extent, provides a margin of microbiological safety. Sensory evaluation by the nine-point hedonic scale showed no detectable loss of organoleptic quality of bread up to 0.6 Mrad, while irradiation to 2.5 Mrad induced unacceptable organoleptic changes.     

Technical and economic potentials of the unconventional extruded dried Arabic bread wastes in broilers diets

Food waste is one of the major global challenges that have adverse socioeconomic and environmental impacts. Therefore, studying food waste utilization potentials and minimizing its negative consequences becomes imperative. This study aims to assess the technical and economic potentials of substituting corn with unconventional extruded dried Arabic Bread waste (EDABW) in broilers’ diets, in terms of broilers’ performance, carcass characteristic, economic net returns, and income over feed cost (IOFC). One hundred eighty unsexed one-day-old broiler birds of Ross breed were distributed randomly in six treatments (0, 20, 40, 60, 80, and 100% EDABW group) of isocaloric and isonitrogenous diets in a completely randomized design with six replicated (5 chicks/replicate). The investigated traits were broilers’ performance (live body weight, total feed intake, total feed conversion ratio, and total weight gain. Other traits such as carcass weight, abdominal fat, edible offal (liver, heart, and gizzard), eviscerated (breast muscles, drum and thigh muscles, and wings) were weighed and expressed based on a live body weight. Results showed that the 20% replacement level of corn with EDABW generated the highest increase in the live body weight and the eviscerated carcass at about 4.24% g and 4.90%, respectively. On the other hand, the economic analysis showed potential reductions in the broilers’ diet cost and the total broilers' production cost as the levels of corn substitution with by unconventional EDABW increased. The reductions were estimated at 5.1%, 6.3%, 8.4%, 9.3%, and 9.9% at substitution levels of 20%, 40%, 60%, 80%, and 100%, respectively as compared to the control diet. The results also showed a potential increase in the net economic returns of broiler meat as the increase in substitution levels ranged between 3.5–06.8% and 4.3–8.3% as compared to the control diets using the average retail and wholesale prices of broiler meats, respectively. In addition, the maximum IOFC was estimated potentially at a 20% substitution level of corn with EDABW. Conclusively, the study results show promising technical and economic potentials for unconventional EDABW in broilers’ diets that could lead to a thriving industry of unconventional broilers’ diets with high net economic returns and maximum IOFC.     

Modulation of immune function in cancer patients

This paper will focus on three aspects of work which we have conducted in our laboratory over the past several years. Firstly, it will present results of studies in which we have found a selective inhibition of suppressor cell function in solid tumor cancer patients treated with cytotoxic drugs. Secondly, it will show that this selective inhibition results in an augmentation of other forms of immune reactivity and, in particular, an enhanced interleukin-2 production and response to this. Finally, it will demonstrate how we have made use of that information to intervene pharmacologically to modulate the immunosuppression which usually follows the use of cytotoxic drugs in solid tumor cancer patients.     

Evidence for immune defects in breast and lung cancer patients

Immunosuppression is often identified in cancer patients. The aim of this study was to evaluate several immune parameters for patients with breast and lung cancer. Immunophenotyping analysis showed that the cancer patients investigated had significantly lower absolute numbers of peripheral blood lymphocytes than controls. The immunosuppression was more evident for the breast cancer subgroup. The most severe immune defect noticed was the marked impairment of IFN- secretion. A shift toward the Th2 phenotype as revealed by assessment of intracellular level of IFN- and IL-4 was also noticed. The secretion of proinflammatory cytokines IL-1 and TNF- in whole blood cultures was not impaired. Although the proportion of activated cells was slightly lower than in the control group, our results showed that both peripheral T lymphocytes and NK cells of cancer patients could be induced to express early activation marker CD69 after ex vivo mitogen stimulation. In conclusion, our study revealed several immune defects in cancer patients. This suggests that an appropriate immunotherapeutical approach might be used to restore compromised immune functions with beneficial effects on both antitumor and general immunity.     

Validation of the Pittsburgh Sleep Quality Index (PSQI) with Arabic cancer patients

Sleep and Biological Rhythms - The Pittsburgh Sleep Quality Index (PSQI), a self-administrated questionnaire, is a frequently used instrument to assess sleep quality in clinical and non-clinical...     

Factors affecting pretreatment immune competence in cancer patients

Summary The assessment of changes in immune competence due to cancer demands carefully controlled studies with simultaneous consideration of other factors such as age, sex, and general ill health. To determine the effect of each factor, immune competence was measured in 112 healthy individuals, 134 patients with benign disease, and 350 patients with cancer (breast, colorectal, and stomach) with a wide spectrum of parameters.In normal subjects, advancing age was associated with a significant reduction in percentage lymphocyte count (LC), absolute and percentage T cell counts, and responses to phytohaemagglutinin (PHA) and pokeweed mitogen (PWM). In patients with benign disease, advancing age was associated with depression of serum IgM levels, absolute and percentage LC, responses to PHA, and delayed cutaneous hypersensitivity (DCH) responses to tuberculin PPD (Mantoux), and dinitrochlorobenzene (DNCB), but elevation of serum IgA levels.No significant sex effects were demonstrated in either group of subjects.The effects of general ill health were determined by comparing individuals in good health (normal subjects and patients with minor benign breast disease) with those who had poor health (patients with significant benign gastrointestinal disease). The latter showed significant depression of DNCB sensitivity and lymphocyte reactivity to PHA, whereas total WBC and LC were significantly elevated.To determine the effects due to cancer, controls were matched for their general state of health and site of disease, in addition to completing all studies prior to any form of therapy. Age differences were corrected for by application of the findings of the above study. This age correction resulted in marked alterations in the significance of observed differences between cancer patients and controls. The previous significance of many differences either disappeared or was reduced, although in two instances significance was attained only after age correction. The only consistent immunodepression observed in the three types of cancer patient tested was impaired reactivity to DNCB. Responses were impaired even in early disease at all three sites.We have shown that the immunodepression exhibited by cancer patients is a summation of the effects due to age, general ill health, and malignancy. Some of the changes previously ascribed to cancer are due to these other factors.     

Effect of psyllium husk and wheat mill bran fractions on the microstructure and mixograph characteristics of Arabic bread

When psyllium husk, wheat bran and germ was added, Incorporation of psyllium and wheat bran may affect the dough structure, dough rheology as well as the final quality of baked Arabic flat bread, which, thus, became important for this study. Scanning Electron Micrographs (SEM) taken on Arabic bread, depicted both intact small and the large starch granules on the outer crust area. This was mainly due to the rapid loss of moisture from the Arabic bread surface during intense baking operation leaving less moisture for gelatinization to take place. With psyllium added to WWF at 0, 3, and 5 % level, the peak time was increased from 3 to 4.5 min. The ascending and descending angle values were more or less identical in all the samples except with wheat germ addition, whereas much lower values (51 to 58°) for these parameters were observed, indicating a faster rate of dough breakdown. With psyllium, fine- and coarse bran addition to WWF, a corresponding increase in peak time was observed. Ascending and descending angles showed similar trends to that of the WWF and psyllium combinations. Use of falling number apparatus is an indirect method of measuring the diastatic enzyme activity in cereal flours. WGF showed lower falling-number values (502 s) than the WWF (607 s). Addition of fine bran to WWF lowered the falling number (607 to 563 s) whereas with coarse wheat bran and germ, these values were increased.     

Circulating immune complexes in patients with breast cancer.

In a retrospective study in women with breast cancer circulating immune complex levels were measured by radioimmunoprecipitation with 125I-Clq. Before operation all the patients showed plasma immune complex levels significantly higher than those in controls. Twelve months after mastectomy patients identified clinicopathologically as having a good prognosis had almost normal levels of immune complexes. By contrast, patients with detectable dissemination on diagnosis or those who died within 22 months after mastectomy had significantly raised plasma levels. The tumour-specific nature of the immune complexes detected remains to be shown and suggestions about the applicability of this test not only for prognosis but also for monitoring the course of malignant diseases need to be confirmed by further investigations.     

Gamma delta T cells are needed for ocular immune privilege and corneal graft survival

It has been recognized for over a century that the anterior chamber of the eye is endowed with a remarkable immune privilege. One contributing component is the Ag-specific down-regulation of systemic delayed-type hypersensitivity (DTH) that is induced when Ags are introduced into the anterior chamber. This phenomenon, termed anterior chamber-associated immune deviation (ACAID), culminates in the generation of regulatory cells that inhibit the induction (afferent suppression) and expression (efferent suppression) of DTH. Since gamma delta T cells play a major role in other forms of immune regulation, we suspected they might contribute to the induction and expression of ACAID. Mice treated with anti-gamma delta Ab failed to develop ACAID following anterior chamber injection of either soluble Ag (OVA) or alloantigens (spleen cells). Additional experiments with knockout mice confirmed that mice lacking functional gamma delta T cells also fail to develop ACAID. Using a local adoptive transfer of DTH assay, we found that gamma delta T cells were required for the generation of regulatory T cells, but did not function as the efferent regulatory cells of ACAID. The importance of gamma delta T cells in corneal allograft survival was confirmed by blocking gamma delta T cells with GL3 Ab before corneal transplantation. While in vivo treatment with normal hamster serum had no effect on corneal graft survival, infusion of anti-gamma delta Ab resulted in a profound increase in corneal allograft rejection. Thus, gamma delta T cells are needed for sustaining at least one aspect of ocular immune privilege and for promoting corneal allograft survival.     

Serial immune testing in surgically resected lung cancer patients

Summary Immunoregulation of phytohemagglutinin (PHA) responsiveness by glass-adherent cells and prostaglandin-synthesizing cells was serially monitored in the peripheral blood mononuclear cells (PBMC) of surgically resected stage I and stage II lung cancer patients entered on a trial of adjuvant immunotherapy. The relationship between immunoregulatory cell function, immunocompetence, and disease relapse was determined. Immunoregulatory activity was measured in PHA-stimulated cultures in the presence and absence of 2 g/ml indomethacin and in the presence and absence of glass-adherent cells. In each instance of disease relapse seen, an increase in immunoregulatory cell function to a level significantly different from normal was observed 3 months prior to or coincident with clinical confirmation of disease recurrence. This was usually associated with a decline in PHA responsiveness. In the patients who did not relapse, the levels of PHA responsiveness and immunoregulatory function persisted within normal limits throughout the course of study. Percentages and numbers of leukocytes and leukocyte subsets and delayed cutaneous hypersensitivity were also monitored in this study, but could not be consistently correlated with early changes in clinical disease status. These data suggest that the development of indomethacin-sensitive and glass-adherent suppressor cells may precede and predict for tumor recurrence in surgically resected lung cancer patients.     

Antigens in immune complexes from patients with breast cancer

Summary Sera and effusion fluids of patients with breast cancer (BC) contain immune complexes (IC). Antigens present in these complexes were isolated as follows: a pool of effusions from patients with BC was fractionated with ammonium sulfate. The proteins precipitating at 40% saturation were further fractionated by filtration through a Sephadex G-200 column. The material recovered in the first peak (molecules larger than monomeric IgG) was brought to pH 3.0 to dissociate the IC, and the mixture was filtered through a column of Sephacryl S-300 at pH 3.0. Proteins smaller than monomeric IgG were collected, radioiodinated, and used as antigens (¹²⁵Ag) to search for corresponding antibodies in sera of patients with BC (BCS) and of healthy individuals (NHS). ¹²⁵Ag was reacted with the sera and the immune complexes obtained were precipitated with an antiserum to human Ig and analyzed by SDS-polyacrylamide gel electrophoresis followed by autoradiography. Both NHS and BCS contained antibodies against two antigens; one of these appeared as a strong band of 17KD, the other as a doublet of approximately 25KD. It is concluded that some of the proteins in the IC from patients with BC are auto-antigens. No BC-specific antigens were identified.     

Perioperative immune responses in cancer patients undergoing digestive surgeries

Aims

We will examine the latest advances in genomic and proteomic laboratory technology. Through an extensive literature review we aim to critically appraise those studies which have utilized these latest technologies and ascertain their potential to identify clinically useful biomarkers.

Methods

An extensive review of the literature was carried out in both online medical journals and through the Royal College of Surgeons in Ireland library.

Results

Laboratory technology has advanced in the fields of genomics and oncoproteomics. Gene expression profiling with DNA microarray technology has allowed us to begin genetic profiling of colorectal cancer tissue. The response to chemotherapy can differ amongst individual tumors. For the first time researchers have begun to isolate and identify the genes responsible. New laboratory techniques allow us to isolate proteins preferentially expressed in colorectal cancer tissue. This could potentially lead to identification of a clinically useful protein biomarker in colorectal cancer screening and treatment.

Conclusion

If a set of discriminating genes could be used for characterization and prediction of chemotherapeutic response, an individualized tailored therapeutic regime could become the standard of care for those undergoing systemic treatment for colorectal cancer. New laboratory techniques of protein identification may eventually allow identification of a clinically useful biomarker that could be used for screening and treatment. At present however, both expression of different gene signatures and isolation of various protein peaks has been limited by study size. Independent multi-centre correlation of results with larger sample sizes is needed to allow translation into clinical practice.     

Hybrid-cell vaccines for cancer immune therapy

Hybrid cells generated by fusing allogenic-presenting cells, such as dendritic cells, with tumor cells are a new tool in cancer immunotherapy which are designed to enhance the immunogenicity of antigenic tumors by presenting the whole spectrum of tumor-associated antigens, by providing the co-stimulatory molecules required for T-cell activation, and by the expression of allogenic MHC molecules for recruitment and activation of T-cell help. This approach has been successfully tested in animal models as well as in clinical phaseI/II trials with various tumors. Besides clinical repsonses, induction of tumor-specific cytolytic T-cells were observed. The electrofusion protocol described here has the advantage of high fusion efficiency, high hybrid-cell viability, as well as high reproducibility, and can be used for various tumor cell types after minor adjustments are made to the instrument settings in order to process large numbers of dendritic cells with consistent efficiencies.     

Monitoring the immune competence of cancer patients to predict outcome

A new era of cancer immunotherapy has brought not only successful cancer vaccines but also immunomodulators, such as those that target checkpoint blockade in order to induce endogenous host immune responses. However, the immune system of cancer patients can be compromised through multiple means, including immune suppression by the tumor and by prior therapies such as chemotherapy and radiation. Therefore, a comprehensive means of assessing patient immunocompetence would seem helpful for determining whether patients are ready to benefit from immunotherapy, and perhaps even which immunotherapy might be most appropriate for them. Unfortunately, there are no standardized tests for immune competence, nor is there agreement on what to measure and what will be predictive of outcome. In this review, we will discuss the technologies and assays that might be most useful for this purpose. We argue for a comprehensive approach that should maximize the chances of developing predictive biomarkers for eventual clinical use.     

Establishment and experimental validation of an immune miRNA signature for assessing prognosis and immune landscape of patients with colorectal cancer

As essential regulators of gene expression, miRNAs are engaged in the initiation and progression of colorectal cancer (CRC), including antitumour immune response. In this study, we proposed an integrated algorithm, ImmuMiRNA, for identifying miRNA modulators of immune-associated pathways. Based on these immune-associated miRNAs, we applied the LASSO algorithm to develop a reliable and individualized signature for evaluating overall survival (OS) and inflammatory landscape of CRC patients. An external public data set and qRT-PCR data from 40 samples were further utilized to validate this signature. As a result, an immune-associated miRNA prognostic signature (IAMIPS) consisting of three miRNAs (miR-194-3P, miR-216a-5p and miR-3677-3p) was established and validated. Patients in the high-risk group possessed worse OS. After stratification for clinical factors, the signature remained a powerful independent predictor for OS. IAMIPS displayed much better accuracy than the traditional clinical stage in assessing the prognosis of CRC. Further analysis revealed that patients in the high-risk group were characterized by inflammatory response, abundance immune cell infiltration, and higher immune checkpoint profiles and tumour mutation burden (TMB). In conclusion, the IAMIPS is highly predictive of OS in patients with CRC, which may serve as a powerful prognostic tool to further optimize immunotherapies for cancer.     

Activity of antibodies recovered from immune complexes of ovarian cancer patients

Summary Ascites fluids from ovarian cancer patients contain immune complexes (IC). Attempts were made to characterize those antigens to which the patient is reacting using antibody recovered from these complexes. Polyethylene glycol (PEG) precipitation and protein A Sepharose 4B affinity chromatography were used to isolate IC. Dissociation of the IC was achieved by G-150 gel filtration in 0.1 M acetic acid, 0.15 M NaCl. Activity of antibody preparations was measured using a binding assay with ¹²⁵I-labeled staphylococcal protein A. Confluent monolayers of various cell lines (including human ovarian and cervical carcinoma lines, human lymphoblastoid cell lines, human and chick embryo fibroblasts) were used. Six of nine antibody preparations isolated from ovarian cancer patient IC contained at least some reactivity against all cell types.Specificity was further defined using cell adsorption assays and polyacrylamide gel electrophoresis. These results indicate what appears to be autoreactivity directed against a normal component(s) of many cells. No evidence for an ovarian cancer-restricted response was shown. Immunoprecipitation analyses showed several polypeptide bands on autoradiograms (49K, 46K, 33K, 25K), which deviated distinctly from the pattern obtained for whole cell extracts.     

Genetically modified immune cells for cancer immunotherapy

正Cancer immunotherapy refers to harnessing the body’s immune system to fight cancer. Cancer immunotherapy has been the hotspot for oncotherapy research since the late 19th century when Dr. Williams Coley used mixed bacteria to boost the body’s immune response to fight cancer. With the rapid development of biotechnology and an increase in the understanding of the body’s immune system, cancer immunotherapy has attracted increased research focus because of its benefits in cancer patients and is considered a leading breakthrough since 2013.