DC preparations for therapy.
This review describes and compares the different DC preparations currently under laboratory and clinical investigation as vehicles for cancer immunotherapy.
Antigens, CD↗
Biomedical subjects
A M Rice
Publications and source records attributed to A M Rice.
Oncology health care professionals' attitudes to cancer: a professional concern.
BACKGROUND: Despite the known benefits of screening, early detection and advances in treatment modalities, negative attitudes to cancer persist among health care professionals, and cancer remains the most feared disease in modern society. Attitudes to cancer may create a barrier to communication between patients and health care professionals, hinder early detection, treatment and rehabilitation, and may influence decision making about referral to specialist services and the selection of appropriate treatments. DESIGN: A descriptive survey was conducted, within a Regional Cancer Centre, to evaluate oncology health care professionals' attitudes towards cancer. Attitudes were measured using the Burns' Cancer Belief Scales. RESULTS: Regardless of gender, profession and clinical experience, all health care professionals displayed persistently negative attitudes towards cancer. No statistically significant difference was detected between gender, profession, clinical experience or specialist education, and although small in number, no major differences were found between group means. CONCLUSIONS: Oncology health care professionals hold negative attitudes towards cancer and changing these attitudes presents a significant challenge. Educational programmes and supportive strategies may alleviate fears and promote a more positive image of cancer. However, such strategies must be based on an understanding of current attitudes towards this phenomenon.
Adult↗
Inhibition of 20 S and 26 S proteasome activity by lithium chloride: impact on the differentiation of leukemia cells by all-trans retinoic acid.
Lithium affects several enzymatic activities, however, the molecular mechanisms of lithium actions are not fully understood. We previously showed that LiCl interacts synergistically with all-trans-retinoic acid to promote terminal differentiation of WEHI-3B D(+) cells, a phenomenon accompanied by the recovery of the retinoid-induced loss of retinoic acid receptor alpha protein pools. Here, we demonstrate the effects of LiCl on proteasome-dependent degradation of retinoic acid receptor alpha proteins. LiCl alone, or in combination with all-trans-retinoic acid, increased cellular levels of ubiquitinated retinoic acid receptor alpha and markedly reduced chymotryptic-like activity of WEHI-3B D(+) 20 S and 26 S proteasome enzymes. Neither KCl nor all-trans-retinoic acid affected enzyme activity, whereas NaCl produced a modest reduction at relatively high concentrations. In addition, LiCl inhibited 20 S proteasome chymotryptic-like activity from rabbits but had no effect on tryptic-like activity of the 26 S proteasome. This effect has significant consequences in stabilizing the retinoic acid receptor alpha protein levels that are necessary to promote continued differentiation of leukemia cells in response to all-trans-retinoic acid. In support of this concept, combination of proteasome inhibitors beta-clastolactacystin or benzyloxycarbonyl-Leu-Leu-Phe with all-trans-retinoic acid increased differentiation of WEHI-3B D(+) cells in a manner that was analogous to the combination of LiCl and all-trans-retinoic acid.
Adjuvants, Immunologic↗
Prolonged ex vivo culture of cord blood CD34(+) cells facilitates myeloid and megakaryocytic engraftment in the non-obese diabetic severe combined immunodeficient mouse model.
A clinical goal for ex vivo expansion of cord blood (CB) CD34(+) cells is to shorten the period of neutropenia and thrombocytopenia following myeloablative therapy and transplantation. Prolongation of cytokine expansion leads to the production of greater numbers of cells, and should have an impact on neutrophil and platelet recovery. Furthermore, expansion of CD34(+) cells should support the continued production of neutrophils and platelets in the 6-week period following transplantation. We tested these hypotheses by characterization of the kinetics (human CD45(+) cells in the blood) and phenotype (CD45, CD34, CD61, CD33, CD19 and CD3) of human engraftment in the non-obese diabetic severe combined immunodeficient mouse (NOD-SCID) following 7 or 14 d of ex vivo expansion of CB CD34(+) cells. Mice transplanted with 14 d cells showed greater percentages of human CD45(+) cells in the blood, bone marrow and spleen than mice transplanted with unexpanded cells or 7 d cells. Prolonging cytokine exposure of CD34(+) cells and transplantation with increasing numbers of input cells facilitated the production of absolute numbers of CD34(+), CD33(+), CD61(+) and CD19(+) cells in vivo. Furthermore, analysis of SCID engrafting potential showed that prolongation of culture duration facilitates in vivo expansion of CD45(+), CD34(+) and CD19(+) cells after transplantation. It is anticipated that prolonged (2 weeks) ex vivo culture of CB will have a beneficial clinical effect.
Analysis of Variance↗
Prior cryopreservation of ex vivo-expanded cord blood cells is not detrimental to engraftment as measured in the NOD-SCID mouse model.
Cytokine-mediated expansion has been proposed and successfully used to facilitate engraftment post transplantation. This study examined whether cryopreservation following expansion has a detrimental effect on the ability of cells to engraft, using the NOD-SCID mouse model. Cord blood (CB) CD34(+) cells were incubated for 7 days with stem cell factor (SCF), flt-3 ligand (FL), and megakaryocyte growth and development factor (MGDF). Expanded CD34(+) cells were transplanted into NOD-SCID mice either fresh or following cryopreservation and thawing. After thawing, recovery of nucleated cells was 94%, of CD34 cells was 63%, and of day-14 progenitors was 17%. The loss of day-14 progenitor cells among the thawed expanded cells did not influence the kinetics of human engraftment in the mouse. Bone marrow (BM) of mice transplanted with thawed expanded CD34(+) cells (14 +/- 3.9%) showed significantly higher levels of human engraftment than mice transplanted with fresh expanded CD34(+) cells (1.5 +/- 0.5%, p = 0.0064). Thawed expanded CD34(+) cells had significantly higher SCID Engrafting Potential (SEP) than freshly expanded CD34(+) cells (p < 0.001). Results suggest that prior cryopreservation does not prevent expanded cells engrafting in NOD-SCID mice.
Animals↗
Conditions that enable human hematopoietic stem cell engraftment in all NOD-SCID mice.
BACKGROUND: Transplantation of human hematopoietic stem cells is the only true test of their long-term repopulation potential. Models are readily available to evaluate murine hematopoietic stem cells, but few exist that allow reliable quantification of human stem cells. The non-obese diabetic-severe combined immunodeficient (NOD-SCID) mouse model enables quantification of human hematopoietic stem cells, but the conditions that permit human engraftment in all animals have yet to be defined. The aims of the project were, therefore, to describe the variables that allow human engraftment in the NOD-SCID mouse model and the techniques that accurately quantify this engraftment. METHODS: NOD-SCID mice that had or had not received 250, 325, or 400 cGy irradiation received cord blood (CB) mononuclear or CD34+ cells i.v. or i.p. Mice were killed 6 weeks after transplantation, and the bone marrow, spleen, and thymus were harvested. Four-color flow cytometric analysis, semi-quantitative PCR, myeloid and erythroid progenitor, and stem cell assays were used to monitor human engraftment. RESULTS: A 250 or 325 cGy and i.v. injection of CB mononuclear or CD34+ cells is required to detect multilineage human engraftment in the bone marrow, spleen, or thymus of NOD-SCID mice. Four-color flow cytometric analysis and semi-quantitative PCR enable accurate detection of 0.1% human cells. Progenitor and stem cell assays provide functional information about the engrafted cells. CONCLUSIONS: Successful development of the NOD-SCID mouse model and techniques to assess human engraftment now allow it to be used reliably to analyze the effects of short-term cytokine exposure on the long-term repopulating capacity of CB stem cells.
Animals↗
Regulation of leptin release and lipolysis by PGE2 in rat adipose tissue.
The role of eicosanoids formed by adipose tissue from rats was examined in the presence of the specific cyclooxygenase-2 inhibitor NS-398. This agent totally blocked the release of prostaglandin E2 (PGE2) by rat adipose tissue over a 24-h incubation in primary culture. The final concentration of PGE2 after 24 h was 12 nM, and half-maximal inhibition of PGE2 formation required 35 nM NS-398. While inhibition of PGE2 formation by NS-398 had no effect on basal leptin release or lipolysis, it enhanced the lipolytic action of 10 nM isoproterenol by 36%. The in vivo administration of PGE2 doubled serum leptin. PGE2 also directly stimulated leptin release by rat adipose tissue incubated in the presence of 25 nM dexamethasone, which inhibited endogenous PGE2 formation by 94%. The inhibition of lipolysis as well as the stimulation of leptin release by PGE2 were mimicked by N6-cyclopentyladenosine (CPA). These data indicate that exogenous PGE2 can stimulate leptin release by adipose tissue when the basal formation of PGE2 is blocked by dexamethasone. However, while the endogenous formation of PGE2 does not appear to regulate basal lipolysis or leptin release, it may play a role in the activation of lipolysis by catecholamines.
Adenosine↗
A1 adenosine receptor activation increases adipocyte leptin secretion.
A1 adenosine receptors (A1ARs) are heavily expressed in adipocytes and influence fat cell metabolism. Because increasing evidence suggests a role for leptin in mediating appetite and fat cell metabolism, we tested whether ALARs regulate leptin production. Rats were treated with the A1AR agonist N6-cyclopentyladenosine (CPA), and changes in circulating levels of leptin and leptin gene expression were examined. Serum leptin levels rose 2- to 10-fold, with peak increases seen 8-16 h after injection of CPA (P < 0.05). In contrast, CPA did not alter steady state levels of adipose tissue leptin mRNA. To assess the influence of endogenous adenosine on circulating leptin levels, rats were also injected with dipyridamole (DPY), an adenosine reuptake blocker. DPY induced 80% increases in serum levels at 8 h after injections (P < 0.05). Supporting the idea that stimulation of leptin production is A1AR mediated, pretreatment with the A1AR antagonist 8-cyclopentyl-1,3-dipropylxanthine completely blocked increases in leptin levels after DPY treatment. To complement in vivo studies, the effect of A1AR activation on leptin secretion was also studied in epididymal fat pad cultures. In cultures, CPA treatment increased leptin secretion by 37% (P < 0.05). Collectively, these data show that the adenosinergic system can increase leptin secretion by directly activating A1ARs in fat tissue.
Adenosine↗
Sexuality in cancer and palliative care 2: Exploring the issues.
The first article in this series discussed the effects of cancer and its treatment of sexual function. However, impaired sexual function may also occur in the absence of any specific physiological change. As well as the patients' perceptions of their disease, the attitudes of society and health care professionals and the environment and culture within health care may contribute to sexual dysfunction in patients with cancer. This article will explore some of the wider issues surrounding sexuality and examine some of the reasons why this subject is so often poorly addressed.
Adaptation, Psychological↗
Etidronate therapy for hypercalcemia in subcutaneous fat necrosis of the newborn.
Subcutaneous fat necrosis of the newborn (SCFN) is characterized by indurated violet skin nodules and, occasionally, life-threatening hypercalcemia. Current treatments of patients with SCFN-related hypercalcemia are often only partially successful and may be associated with prolonged hypercalcemia. We now report the use of etidronate, a bisphosphonate, to control hypercalcemia in an infant with SCFN.
Etidronic Acid↗
An introduction to radiotherapy.
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Humans↗
Cytokine-mediated expansion does not deplete cord blood cells with stem cell characteristics.
Cord blood (CB) has been successfully used to regenerate the hematopoietic system after myeloablative therapy. We investigated whether cytokine mediated expansion depletes CB of cells with stem cell characteristics. CB mononuclear cells (MNC) were enriched for quiescent (primitive) stem cells by incubation with 25 micrograms/ml 5-Fluorouracil (5-FU) and control CB MNC were incubated with media alone. Cells were then incubated for 7 days with Interleukin-1 (IL1)+IL3+Stem Cell Factor (SCF) and progenitor content, cell cycle status, nucleated cell count, immunophenotype and resistance to 25 micrograms/ml 5-FU (primitive stem cells) were evaluated before and after cytokine exposure. Incubation with IL1+IL3+SCF caused an increase (fold expansion) in committed (28.6 +/- 8.1), immature (5.8 +/- 1.8), and primitive progenitors (4.1 +/- 0.8) among control CB MNC compared to a decrease in committed progenitors (0 +/- 0) but an increase in both immature (8.4 +/- 4.8) and primitive progenitors (7 +/- 2.9) among 5-FU resistant CB MNC. An increase in the proportion of CD34+ cells occurred in both fractions. Expanded control CB MNC showed a significant increase in numbers of 5-FU resistant committed (p = 0.024), immature (p = 0.014) and primitive progenitors (p = 0.01) as compared with fresh CB MNC. Re-exposure of 5-FU resistant expanded CB MNC to 5-FU shows growth of some immature and primitive progenitors. Cytokine-mediated expansion of untreated and quiescent CB cells is possible and cytokine-mediated expansion does not deplete CB cells with stem cell characteristics.
Antigens, CD34↗
Evaluation of a monoclonal IgM antibody for purging of bone marrow for autologous transplantation.
A monoclonal antibody of the IgM class, reacting with the CD9 (p24) antigen is described. The antibody (FMC27) is cytotoxic against cells of the common type of acute lymphoblastic leukaemia (c-ALL), giving killing at higher dilutions than an IgG antibody (FMC8) against the same antigen. FMC27 and FMC8 recognise different epitopes, and FMC27 may thus be used in a cocktail together with FMC8 and an antibody against the c-ALL antigen, WM21. Furthermore, the IgM antibody can be coated directly onto magnetic microparticles for magnetic purging, unlike the IgG antibody which must be used in a two-layer procedure.
Antibodies, Monoclonal↗
Comparative specificity and sensitivity of routine cytologic examinations and the Gravlee jet wash technic for diagnosis of endometrial changes.
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Adenocarcinoma↗